Wild and Exotic Animal Ophthalmology - Zoologia (2025)

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Fabiano Montiani-FerreiraBret A. MooreGil Ben-Shlomo EditorsVolume 1 Invertebrates, Fishes, Amphibians, Reptiles, and BirdsWild and Exotic Animal OphthalmologyWild and Exotic Animal OphthalmologyFabiano Montiani-Ferreira • Bret A. Moore •Gil Ben-ShlomoEditorsWild and Exotic AnimalOphthalmologyVolume 1: Invertebrates, Fishes, Amphibians,Reptiles, and BirdsEditorsFabiano Montiani-FerreiraVeterinary Medicine DepartmentFederal University of ParanáCuritiba, BrazilBret A. MooreCollege of Veterinary MedicineUniversity of FloridaGainesville, Florida, USAGil Ben-ShlomoCollege of Veterinary MedicineIowa State UniversityAmes, Iowa, USAISBN 978-3-030-71301-0 ISBN 978-3-030-71302-7 (eBook)https://doi.org/10.1007/978-3-030-71302-7# Springer Nature Switzerland AG 2022This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material isconcerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproductionon microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation,computer software, or by similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does notimply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws andregulations and therefore free for general use.The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed tobe true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty,expressed or implied, with respect to the material contained herein or for any errors or omissions that may have beenmade. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Cover Images: Top large image: Pacific chorus frog (Pseudacris regilla) # Bret A. Moore. Small square images fromleft to right: Box crab (unknown species) # David G. Heidemann, Octopus (unknown species) # David G.Heidemann, Seahorse (unknown species) # David G. Heidemann, Tokay gecko (Gekko gecko) # Bret A. Moore,Veiled chameleon (Chamaeleo calyptratus)# Bret A. Moore, Southern ground hornbill (Bucorvus leadbeateri) # ZigKochThis Springer imprint is published by the registered company Springer Nature Switzerland AG.The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerlandhttps://doi.org/10.1007/978-3-030-71302-7In remembrance of our friend.Say not in grief ‘he is no more’ but in thankfulness that he was—HebrewproverbThere is so much to be grateful for when it comes to Gil Ben-Shlomo, whetheryou knew him well or simply met this gentle giant at a conference somewherearound the world. Gil’s bright smile, keen intellect, hearty laugh, and charismawould always light up a room and bring joy to people around him.Our beloved Gil was taken from this world far too soon. He passed awayunexpectedly at the age of 50, leaving behind his wife of 20 years, Anna, his twodaughters Roni and Noam, his extended family, and two Boxer dogs.Undoubtedly, Gil’s family was his greatest accomplishment, a daily source ofpride, and the foundation for him to achieve so much in life.Gil Ben-Shlomo (DACVO 2012) earned his DVM and PhD in Neurobiologyfrom the Koret School of Veterinary Medicine at the Hebrew University ofJerusalem, Israel. He completed his comparative ophthalmology residency atthe University of Florida (2007–2010) and joined the faculty at Iowa StateUniversity as Assistant Professor in 2010, progressing to Associate Professorwith tenure in 2016. As a teacher, Gil served as a role model for students andresidents through his professionalism and ethical standards. His passion forveterinary ophthalmology fueled his approach and success in teaching the nextgeneration of veterinarians and veterinary ophthalmologists. His innovativeresearch in retinal neurodegeneration had a significant impact on both theveterinary and human realms, providing a bridge from the bench top to thepatient. In the clinic, Gil was always known for the generous number of treatshe would give his patients, his warm and welcoming demeanor, his outstandingclinical and surgical skills, and his wonderful smile. In 2019, Gil left Iowa Statefor an Associate Professor position at Cornell University, where he quicklybecame an integral member of the Ophthalmology service. Gil was also activeon the international scene, serving as the president of the International Societyof Veterinary Ophthalmology, as an editorial board member for the journalVeterinary Ophthalmology, and as a member on committees for variousorganizations. Most recently, Gil’s passion and dedication to the profession ledhim to serve as an associate editor for two authoritative textbooks, VeterinaryOphthalmology (6th edition) and Exotic and Wild Animal Ophthalmology.Gil was a doting father, devoted husband, loving brother and son, and a dearfriend to many. Gil’s impact on my life was a true blessing that I cherish everyday; he made me a better ophthalmologist, researcher, teacher, and, moreimportantly, a better person. Reading the many messages of condolence andthe outpouring of love for Gil, it comforts me to know that he had the samepositive impact on countless other people around the world.May our fond memories of Gil, and our gratitude for his exceptional legacy,inspire us to live each day to its fullest, be kind to one another, hold our lovedones very close, and pursue our passion for veterinary ophthalmology withenthusiasm and countless smiles.Eternal thanks to Gil for his ingenuity and insight in coediting the incredibletextbook before you.With love,Lionel Sebbag, DVM, PhD, DACVOKoret School of Veterinary MedicineHebrew University of Jerusalem, IsraelForewordThis work addresses a need that has been long-standing in comparative ophthalmology.Namely, the creation of a single reservoir of information, focused on wild and exotic animalspecies, from which both comparative vision scientists and clinical veterinarians (from com-prehensive practitioners to wildlife and exotic specialists to comparative ophthalmologists) candrink. There are expansive works on comparative vision and ocular structure (Walls 1942,Rochon Duvigneaud 1943, Polyak 1958, Gregory and Cronly-Dillon 1991, Schwab 2012, andWarrant and Nilsson 2006, among others), but these typically lack specific critical details mosthelpful to a clinician contemplating the wild or exotic patient in front of them with an oculardisorder. Similarly, in the comparative clinical literature, there are numerous mini-reviewsavailable on specific groups of animals (often focused on a vertebrate class or order within aclass), and there are a limited number of excellent overviews provided in textbooks of veteri-nary ophthalmology, but there has, to date, not existed a comprehensive resource thatsummarizes the available literature while providing practitioner insights on evolution, environ-mental niche, relevant aspects of captive management (in the context of ocular disorders),ocular functional morphology, and known ocular diseases and surgical procedures across thespectrum of wild and exotic patients seen by comparative ophthalmologists. This work goes along way toward filling that void.The editors have selected a diverse cast of experts to assemble the encyclopedic informationpresented in this text. Notably, and appropriately, not all authors are veterinaryophthalmologists, enabling the presentation of the best pertinent information available. Allchapters strive to provide a balance of the comparative basic functional morphology and visualecology with the known clinical entities and reported therapeutic strategies. The text iscomplementedsupportive cells(Fig. 2.7). The photoreceptors have inner segments andrhabdomes, which are similar to outer segments and arelight-sensitive organelles. The supporting cell function isunknown, but they exist around the photoreceptors(Breneman et al. 1986). Similar to vertebrates, the retinadoes store and cycle Vitamin A, however, this appears tooccur in just the photoreceptors and in a much less complexmanner in cephalopods than in vertebrates (Liou et al. 1982)(Taba et al. 1989). Unlike vertebrates, light directly hits themuch larger outer segments of the photoreceptor retinal cells(Hara and Hara 1972). There are two visual pigment cells incephalopods: rhodopsin and retinochrome (Hara and Hara1967).The nerve fibers of the cephalopod are posterior to theretina (in contrast to the vertebrate eye) and therefore do notcreate a blind spot when exiting the eye as the vertebratenerve fibers do (Fig. 2.7). While the cephalopod retina ismissing some of the processing cells present in the vertebrateretina, it is theorized that this processing occurs in the opticlobes of its brain instead (Young 1962). One studysupporting this theory, showed that there are highconcentrations of an amino acid, D-aspartate in both theretina and the optic lobes and that concentrations of thisamino acid change based on light intensity (D’aniello et al.2005).Fig. 2.6 Histologic section of Humbolt squid Dosidicus gigas eyesdemonstrating relative complexity including the well-developed uvealtract (arrowheads), spherical lens (asterisks), and retina (arrows).Stain ¼ Hematoxylin & Eosin. Courtesy of the Comparative OcularPathology Laboratory of Wisconsin16 J. L. Gjeltema et al.Despite being brightly colored themselves, cephalopodshave historically not been thought to see color as they onlyhave one photoreceptor cell, which prevents color distinction.Nonetheless, there is debate about this and it has recentlybeen postulated that the unique pupil shape can help to scatterdifferent wavelengths of light to allow specific colors to beprocessed by the retina and brain (Stubbs and Stubbs 2016).Additionally, there is recent information that the skin mayplay a role in color detection (Kingston et al. 2015) (Ramirezand Oakley 2015). The process through which this may occuris complex and not fully understood, but there are photore-ceptor components in the skin chromatophores that are usedto create diverse and changing skin color patterns that serveas camouflage. This study showed that the skin color willchange when exposed to different light colors, particularlyblue light. Although the degree that cephalopods distinguishcolor is debated, some cuttlefish and octopuses, are able todistinguish polarized light, something that many other spe-cies including humans cannot do (Fig. 2.8) (Hanke andKelber 2020) (Temple et al. 2012).Clinical ProblemsCephalopods, similar to other species can develop a range ofophthalmic conditions including corneal ulcers, anterior uve-itis, cataracts, retinal disease, and phthisis bulbi. Retraction ofthe skin around the eyes due to a loss of body mass can be asign of senescence in the octopus (Anderson et al. 2002).Corneal disease is most often due to either trauma or envi-ronmental causes such as UV damage or water qualityfluctuations including changes in nitrates, ammonia,phosphates, and salinity. Lenticular disease is often due toaging, trauma, or environmental changes such as UV lightdamage. Trauma is certainly a common etiology of oculardisease, and a history of trauma can often be deduced byvisualization of a phthisical eye in wild cephalopods, not anuncommon sequelae to severe trauma (Fig. 2.9a). Occasion-ally, symbiotes can be found cleaning the ocular surface, suchas Bruun’s cleaning partner shrimp Urocaridellaantonbruunii (Fig. 2.9b), and should not be confused with acorneal parasite. However, some copepod species can beFig. 2.7 Histologic cross-section of the retina of an octopusdemonstrating similar but inverse organization to the retina ofvertebrates. Note that the distal rhabdomeric receptor segments withsupporting cells (1) are located immediately under the internal limitingmembrane rather than on the posterior side of the retina as in vertebrates.More posterior, the proximal rhabdomeric receptor segments (2) arevisible. Finally, the nerve fiber layer of efferent axons (3) is on theposterior side of the retina instead of anterior. Stain ¼ Hematoxylin &Eosin. Courtesy of the Comparative Ocular Pathology Laboratory ofWisconsin2 Ophthalmology of Invertebrates 17Fig. 2.9 (a) Giant Pacific octopus Enteroctopus dofleini with a phthisi-cal end-stage eye. Note that chromatophores cover the densely fibroticand small end-stage eye. This eye was nonvisual. (b) A Bruun’scleaning partner shrimp Urocaridella antonbrii cleaning the ocularsurface of a Giant Pacific octopus. (b)—Used with permission fromNatalie11345, Shutterstock.comFig. 2.8 Gross photograph of the Cuttlefish globe demonstrating its structural similarity to the vertebrate eye. Courtesy of the Comparative OcularPathology Laboratory of Wisconsin18 J. L. Gjeltema et al.http://shutterstock.comattached to the corneal surface of some cephalopods,inflicting corneal damage as a result.GASTROPODAIntroduction and Natural HistoryThe gastropods are a class in the phylum Mollusca andinclude over 80,000 marine, fresh water and terrestrial spe-cies. The group includes abalone, conchs, nudibranchs, seahares, slipper shells, slugs, snails, and whelks, among manyothers. All gastropods have a ventrally flattened foot thatprovides locomotion along the various surfaces of theirhabitats. Most are aquatic and have a well-developed headwith eyes and other sensory organs, an external shell, themuscular foot, and a respiratory chamber containing gills. Asthe molluscan class with the most species and morphologicvariety, it is hard to make generalizations for the entire group.One need only examine a common garden slug (lacking gills,a shell, and terrestrial), to appreciate the exceptions to thenorm and diversity within the taxon. One anatomical anddevelopmental feature all gastropods have in common is180� torsion of the visceral mass as it relates to the foot(Ruppert et al. 2004). This event occurs in the larval formand in some groups a secondary detorsion occurs (Ruppertet al. 2004). The anatomical consequences of torsion havepresented the group with many functional challenges that arebeyond the scope of this chapter.The use of gastropods as laboratory animals and in aqua-culture is limited but does occur. They are, however, impor-tant display and food animals. Investigators working on thesea hare, Aplysia californica, were awarded a Nobel Prize formedicine or physiology in 2000 (Nobel Media AB 2020 n.d.).Finally, it should be mentioned that with the advent ofmolecular taxonomy, and an ongoing surge of work in thisarea, the taxonomic playing field is shifting due to some“related groups” being found as paraphyletic. One result ofthis is the grouping of a large number of invertebrate phyla,including the annelids, brachiopods, bryozoans, cnidarians,crustaceans, mollusks, and platyhelminthes, into a largegroup called the Lophotrochozoa. A recent publicationreviews the topic (Randel and Jékely 2016) (Fig. 2.10).HandlingGastropods are generally easy to restrain as they are slowmoving and can be secured manually or with a protectivecontainer or device. Handling shelled gastropods, whethermarine, terrestrial, or freshwater presents little risk to theanimal or handler. The shell-less gastropods (nudibranchs,sea hares, slugs) are more sensitive and may require wearinglatex gloves and/or handling them in a transparent plasticbag. Most gastropods are harmless to humans but somemembers of the tropical genus Conus can inflict seriousinjury or even death with small toxic “harpoons” that aremodified from radular teeth (Binghamet al. 2012).In order to perform a thorough ophthalmic examination,sedation or anesthesia may be required. Garden and pondsnails can be anesthetized with 5% ethanol or menthol (Floreset al. 1983) or inhalant agents like isoflurane (Girdlestoneet al. 1989). A commercial 10% Listerine® solution (ethanol21.9%, menthol 0.042%) in normal saline is commonly usedto anesthetize pond snails (Lymnaea) in research settings(Woodall et al. 2003). Magnesium chloride (30 g/L) hasbeen used successfully in the queen conch, Strombus gigas(Acosta-Salmón and Davis 2007). A recent study determinedthat immersion in 5% ethanol is suitable to anesthetize thegiant African land snail, Acathina fulica (d’Ovidio et al.2019). The authors found that 29/30 animals survived thetrial, in which most animals were induced in about 25 minutesand recovered in an average of 20 minutes. It should be notedthat ethanol immersion was determined to cause stress for theAustralian marine snail, Dicathais orbita, and the authors ofthis multi-agent study concluded that 0.5 M magnesiumchloride was effective at allowing for sex identification andresulted in minimal stress (Noble et al. 2009).Terrestrial snails can be anesthetized with inhalantisoflurane or sevoflurane, though some type of anestheticchamber is required. Ideally, this would include the abilityto provide fresh air and anesthetic scavenging (Girdlestoneet al. 1989). The mean anesthetic concentration of isofluranein Lymnaea, the pond snail, is reported as 1.09 (Girdlestoneet al. 1989). When used for induction, this takes less than10 minutes, but an excitatory period is commonly observed.Inhalant anesthesia presents the disadvantage of the need toremove the patient from the chamber for the procedure,which may result in anesthetic depth fluctuation and environ-mental release of anesthetic gases.Intracoelomic administration of magnesium sulfate ormagnesium chloride can be used for large marine gastropods,like the California sea hare, where induction is fast (less than5 minutes) and leads to good muscle relaxation (Clark et al.1996).Clinical TechniquesThere is very little in the literature that could be classified asveterinary clinical techniques for this group of invertebrates.Numerous studies have been published that investigate eyeregeneration following amputation (see Anatomy and Physi-ology section) but while surgical, these are not clinical2 Ophthalmology of Invertebrates 19studies to benefit the animal. Gastropods and other molluscsare important animal models for the study of the human eyeand associated disease, but again, the techniques can best bedescribed as basic science and not for clinical application(Serb 2008).Ophthalmologic Anatomy and PhysiologyIt is important to note that image formation depends on thepresence of photoreceptors, and image quality is affected byphotoreceptor numbers and density (Ruppert et al. 2004).Fig. 2.10 Planktonic eye larvae in a number of invertebrate groups. Used with permission from “Randel and Jékely (2016). Phototaxis and theorigin of visual eyes. Philosophical Transactions of the Royal Society B: Biological Sciences, 371 (1685), 20150042”20 J. L. Gjeltema et al.Most aquatic invertebrates, whether because of size, or theirnatural history, have relatively few photoreceptors and hencepoor eyesight when compared to vertebrates (Ruppert et al.2004). The eyes of gastropods vary between a simplepigmented cup that can detect light and shadows, as thosefound in limpets, to more complex forms with a lens andnumerous photoreceptors, found in heterobranchs, a largetaxonomic grouping that contains nudibranchs, sea hares,slugs, and snails (Ruppert et al. 2004) (Gillary and Gillary1979) (Bobkova et al. 2004). Figure 2.11 illustrates two eyetypes, one basic, and the other more sophisticated, among thegastropods (Serb and Eernisse 2008). Even within a subgroupof gastropods, such as the snails, great diversity in the eye canbe appreciated (Fig. 2.12). In many cases the eye is located ona stalk (eyestalk) and this structure may be fused with orseparate from the multisensory, bilaterally symmetrical, andcephalic tentacle (Ruppert et al. 2004; Zieger and Meyer-Rochow 2008). To what extent gastropods are able to formclear optical images is up for debate. Some feel that aquaticpulmonates (snails) have better vision than their terrestrialcounterparts, largely due to their need to find thin plant stalksto climb in order to breathe (Gál et al. 2004). There is goodevidence that both terrestrial and aquatic gastropods relymore on chemoreception than vision to navigate their envi-ronment (Chase 2001; Emery 1992; Gál et al. 2004). Ziegerand Meyer-Rochow (2008) provide a thorough review ofpulmonated gastropod eyes.Some gastropods have the ability to regenerate eyes,although, the new eye is usually smaller than the original(Hughes 1976). In marine conchs (Strombus sp.), ananatomically functional eye develops in just 14 days aftersurgical amputation (Hughes 1976). Other studies foundsimilar results following amputation of eyes in other aquaticgastropods (Bever and Borgens 1988; Flores et al. 1983;Gillary 1972; Gillary and Gillary 1979).CrustaceaIntroduction and Natural HistoryCrustacea is a group of arthropod invertebrates that includescrabs, lobsters, crayfish, shrimp, woodlice, fish lice, andbarnacles. Crustacean species are ecologically valuable andare often kept for exhibition or educational purposes inaquaria. They are also economically valuable and are fre-quently farmed or harvested for human consumption.Crustaceans are generally distinguished from otherarthropods by the branching pattern of their limbs and forsome by their larval life stages. Many crustaceans have larvallife stages during development, such as the copepod naupliusstage, while other crustaceans emerge from eggs as smallversions of adults. These tiny planktonic forms often grazeon microscopic plants and are an important part of foodchains for animals like birds, fish, and whales. As adults,crustaceans fill a variety of ecologic niches ranging frompredatorial crabs to parasitic copepods.Anatomically, the general crustacean body organizationconsists of segments called somites. Fused somites formthree major body sections: the cephalon (head), thorax, andabdomen. In some crustaceans, the cephalon and thorax arefused together into a cephalothorax. Segmented appendagesextend from these somites to form limbs, antennae, andmouthparts. A tail-like segment called a telson may also bepresent at the posterior aspect of the animal. As like otherarthropods, the exterior cuticle forms an exoskeleton, whichat the cephalothorax is often calcified and forms a hardprotective carapace. The exoskeleton must be molted offperiodically as the animal grows. In some crustacea such asparasitic copepods, there is wide sexual dimorphism withhuge size differences between the much smaller males andFig. 2.11 Two eye types, one basic (a), and the other more sophisti-cated (b), among the gastropods. Used with permission from, “Serb andEernisse (2008). Charting evolution’s trajectory: Using molluscan eyediversity to understand parallel and convergent evolution. Evolution:Education and Outreach, 1(4), 439–447”2 Ophthalmology of Invertebrates 21much larger females. The internal anatomy consists of thegut, aorta, heart, stomach, nerve cord, brain (also calledsupraesophageal ganglion). Individuals are typically eithermale or female, but there are some groups, like the barnacles,that have both male and female reproductive organs.HandlingCrustaceans are relatively easy to handle although glovesshould ideally be worn. Many crustaceans such as barnaclesare easy to grasp gently for external examination. Somecrustaceans such as crabs and lobsters have pincers or chelaethat can pinch, crush, and injure the handler. Somecrustaceans such as prawns have more than one set of chelaethatmay be less obvious to the casual observer, and care toshield the ophthalmologist from these appendages is impor-tant for safety during ophthalmologic evaluation. To examinethe eye, ideally the animal itself is held securely by thecarapace by an assistant and the eye exam is performedquickly, with slit lamp biomicroscopy. As complete restraintof the animal may be challenging, it is important to be fastwith the eye exam itself.In some cases, anesthesia may be appropriate to facilitateexamination or diagnostics. A variety of anesthetic agents,including both injectable formulations and anestheticbaths, have been used successfully in crustaceans. Baths oftricaine methanesulfonate or eugenol/clove oil have beeneffective for some species as well as injectable lidocaine,ketamine, or xylazine(“Clinical Anesthesia and Analgesia inInvertebrates,” 2012; Lewbart 2022).Clinical TechniquesA variety of clinical techniques have been described for usein crustaceans. A thorough review of water qualityparameters and husbandry is an essential part of a compre-hensive evaluation. Collection of hemolymph may beperformed at arthrodial membranes, which are softer sectionsFig. 2.12 The microanatomical differences between the eyes of sixspecies of aquatic and terrestrial snails are illustrated here. FromBobkova, M. V., Gál, J., Zhukov, V. V., Shepeleva, I. P., & Meyer-Rochow, V. B. (2004). Variations in the retinal designs of pulmonatesnails (Mollusca, Gastropoda): Squaring phylogenetic background andecophysiological needs (I). Invertebrate Biology, 123(2), 101–115.Used with permission22 J. L. Gjeltema et al.of exoskeleton that form flexible joints between more rigidportions, or at the location of the heart for some species(Lewbart 2022). Biopsy of gills or accessible exoskeleton/cuticle for cytologic evaluation, culture, or histopathologicreview may also be helpful. Depending on the species ofcrustacean and the accessibility of the eyes, the ophthalmicexam can be performed as with other species using a slit lampbiomicroscope, tonometer (rebound preferred), fluoresceinstaining, and indirect ophthalmoscopy.Most evidence-based therapeutic options for crustaceanshave been developed for use in aquaculture, and it is impor-tant to note that many species are considered food animalswith regulatory requirements that must be met when prescrib-ing medications. As crustaceans can often be handled andremoved from the aquatic environment relatively easily,treatment of an individual animal (as opposed to an entiresystem) with topical treatment can be performed. Topicaladministration or baths of antibiotics can be used in casesof wounds or suspect infection of the compound eyes.Animals shown to be infected with communicablepathogens should be removed from the group enclosure andquarantined during treatment. If multiple animals areaffected, the entire system should be treated and any newanimals kept separate. As with other aquatic invertebrates,group treatment of crustaceans is often most easily accom-plished via feed or treatment of the water. For any tank-basedtreatments, the impacts of the treatment on other species inthe enclosure as well as the bacteria of the biofilter areimportant factors to consider. Very limited evidence-basedand clinically-oriented scientific reports outside of thoseestablished for aquaculture are available in the veterinaryliterature describing case management or interventionaltreatments for crustaceans.Ophthalmologic Anatomy and PhysiologyOrbit/GlobeMany crustaceans have compound eyes similar to insectssuch as flies (Fig. 2.13). These intricate organs have multiple,generally thousands, of individual eyes in a tube-like shape(called ommatidia) that extend from a central optic nerve(Fig. 2.13 b-d). Each one of these tubes is actually an eye inand of itself with a cornea, lens, and photoreceptors (Fig. 2.13d). Each eye is processing an image that is compiled like amosaic of relatively good image quality. The shape and sizeof the entire compound eye and is species dependent andrelatively small, measuring 67 mm in length and 2.5 mm indiameter for Squilla (Schönenberger 1977). The eye stalksare capable of movement and in mantis shrimp tend to movespontaneously without apparent coordination between theeyes. The eyes move around 3 axes (Land et al. 1990).Some of the stomatopods have compound eyes that can rotateup to 70 deg. around the stalk axis (Marshall et al. 1991).They also can move in a coordinated pattern, and are capableof eye movements of three different classes: scanning, opto-kinetic, and targeting/tracking (M. F. Land et al. 1990). Theommatidia of compound eyes have many differentadaptations for various ecological niches. For example, insome cases, the face of an individual ommatidium can changebased on the position of other ommatidia to face differentobjects (Schwab 2011). Some other adaptations of compoundeyes include antireflective properties based on changes incurvature and an additional layer across the cornea thatallows for better light absorption (Schwab 2011).The eyes themselves are posteriorly attached directly tothe nerve and the peripheral corneas of the ommatidia areattached to the exoskeleton. There are no specific adnexalstructures in crustaceans; however, there is a very importantgland historically called the “eye-stalk gland” and nowreferred to as the sinus gland that is responsible for releasinga chromatophototropic hormone (Abramowitz 1937). Thisgland is located within the ganglionic region of the eye andis a major neurohormonal secretor for crustaceans. It has alarge role in regulating metabolism and other physiologicfunctions with six areas it regulates including 1) light adap-tive responses of retinal pigments, 2) heart rate, 3) metabo-lism, 4) reproduction, 5) regeneration growth, and molting,and 6) somatic pigmentation (Smith 2000).CorneaThe cornea is the outer clear refractive layer of the ommatid-ium (Fig. 2.14). It abuts the pigment cells and is the externalcomponent of the ommatidium. The cornea itself is about20 microns thick and similar to a vertebrate cornea, is multi-layered (Hariyama et al. 1986).Uvea/LensIn the apposition compound eye (see optics) such as those ofsome shrimp (Fig. 2.13 a), there can either be one lens(a crystalline cone) focusing light onto the rhabdom or multi-ple lenses focusing light and forming images which are thenprocessed in the brain. The lens itself is comprised of crystal-line cones which are directly posterior to the cornea. Fourdifferent cells are involved in the lens composition. In the eyeof the isopod, Ligia, the crystalline cones are 100 micronslong and 35 microns in diameter (Hariyama et al. 1986). Theuvea is essentially pigmented cells that line the crystallinecone of the lens an a tube-like posterior structure that is filledwith photoreceptors and the rhabdom. This terminates in theoptic nerve. The function of these pigment cells is to blocklight coming from different angles so that each ommatidiumonly responds to the visual information directly in front ofit. As these ommatidia are all sandwiched together, the pig-ment cells are used for multiple ommatidia and one cell willline three ommatidium.2 Ophthalmology of Invertebrates 23The appearance of dark areas observed grossly “deep”within compound eyes of insects are called “pseudopupils”and are caused by smaller regional inter-ommatidial anglesindicating areas of enhanced resolution for the animal(Fig. 2.13 b, c). The same structures are present in otherinvertebrate groups with ommatidia, such as insects (seebelow). The pattern formed by pseudopupils varies by spe-cies or group and depends on the natural history of theanimal.Retina, Vision, and OpticsThe processing layers of the ommatidium include the rhab-dom and photoreceptor cells which transmit the image to theoptic nerve at the back of the rhabdom. The rhabdom isactuallya transparent tube at the center of the ommatidiumthat is lined by retinula (R cells), which are the photoreceptorcells. The number of R cells varies per species; in Ligia, thereare 8 retinula cells, one of which has a dendrite that extendsinto the rhabdom (Hariyama et al. 1986). Some crustaceansFig. 2.13 Compound eyes of Crustacea. (a) Peacock mantis shrimpOdontodactylus scyllarus. (b) Mantis shrimp eye under greater magnifi-cation, demonstrating some of the thousands of ommatidia. (c) Macro-scopic photograph of one compound eye of a brown box crabLopholithoides foraminatus. (d) Histopathology image (H and Estained) of the compound eye of a krill. Each ommatidium is lined upnext to the other, the cornea is at the outermost aspect and the anatomyfrom cornea to retina (photoreceptors) is visible. Note the pseudopupils(b, c) visible as dark spots appearing as pupils that are actually smallerregional inter-ommatidial angles. Stain in (d) ¼ Hematoxylin & Eosin.(a–c)—Courtesy of David G. Heidemann. (d)—Courtesy of the Com-parative Ocular Pathology Laboratory of Wisconsin24 J. L. Gjeltema et al.have tapetal cells which have reflective crystals that form aconcave mirror that line the inside of the tubes and forms afocused image on the retina (Andersson and Nilsson 1981).The photoreceptors of the compound eye of the crustaceanare capable of distinguishing differences in light intensity aswell as color. The images produced by a compound eye aredecreased in resolution compared to a single-aperture eye,but they possess some advantages over single eyes includinga large field of view (Fig. 2.15), an ability to detect polarizedlight in some cases (Lindström 2000), and the ability todiscern fast movement.Image processing in compound eyes is of two forms,either apposition eyes where multiple inverted images areformed or superposition eyes, where a non-inverted singleFig. 2.15 Crab eyes showing the wide field of view that’s possible with some of the crustacean compound eyes. Courtesy of David G. HeidemannFig. 2.14 Photomicrograph demonstrating the compound eye of a krill.The top curved undulating layer is the corneas lined up from each of theommatidium. Each convex mound (marked by an asterisk) is one corneafrom one ommatidium. Stain ¼ Hematoxylin & Eosin. Courtesy of theComparative Ocular Pathology Laboratory of Wisconsin2 Ophthalmology of Invertebrates 25image is created. Superposition eyes can form images fromeither reflection or refraction of the light.Some of the more advanced compound eyes, such as thoseof the stomatopods (mantis shrimp), essentially have trinocu-lar vision with the ommatidia divided into different func-tional groups based on location. There are two peripheralgroups or hemispheres and one central or mid-band regionof 6 rows (Marshall et al. 1991). Some of the mid-band rows(5–6) and the peripheral hemispheres are sensitive to polari-zation whereas some of the other mid-band rows (1–4) areused more for color vision (Marshall et al. 1991). Themid-band rows are relatively large compared to thehemispheres. For example, the 6 mid-band rows each occupy5% of the retinal volume (for a total of 30%) in some shrimpcompared to the 65 rows of the hemispheres which eachoccupy about 1% of the retinal volume.From the outside, you can see there is a reflection andimage formation on the eye itself (Fig. 2.13 b showsexamples of this). This is because there is a superpositionimage formed by reflection in some of the eyes ofcrustaceans. Many prawns, crayfish, and lobsters have thesereflecting superposition compound eyes (Nilsson 2013).While all the corneas and lenses work together to take lightand direct it specifically to form a single image on thereceptor layer, in many cases, the tapetum can then reflectthe light back out and cause this reflection to glow (MichaelF. Land 1976).Clinical ProblemsSimilar to other aquatic animals, health problems typicallyfall into a few different categories. These include 1) trauma,2) infection (bacterial, viral, fungal, parasitic), 3) environ-mental/toxic (particularly due to water quality fluctuations),4) aging/degenerative, and 5) congenital. For example, thecorneas of the compound eyes can be damaged via directimpact including conspecific or predatorial damage. Thecrystalline lenses can suffer damage from the same insult ifit is significant enough or it can also suffer damage fromeither degenerative changes (sclerosis/cataract) or environ-mental issues such as UV light.One study of farmed shrimp that were otherwise ill, found“suppurative” inflammation of the eye in more than 50% ofthe moribund shrimp. Other less common conditions thatoccurred included granuloma of the eye where the granulomaeffaced the ommatidia, ganglia, and internal eye structuresand malacia of the eye causing necrotic nervous tissue. In thisfarmed shrimp study, Vibrio spp. and a virus (similar toLymphoid Organ Virus, Gill-Associated Virus, and Yellow-Head Virus) were found in the affected shrimp (Smith 2000).There is another viral disease seen in fish and shrimp inaquatic environments called Infectious Hypodermal andHematopoietic Necrosis (IHHN) that damages the nervesand ganglia of the eye. Any of these eye diseases, eitherbacterial, fungal, or viral can cause significant damage; and,given the importance of the eye in the overall function andmetabolism of crustaceans, it is critical that these diseases areprevented if at all possible. There is not much in the literatureabout eye diseases of shrimp, implying either a lack ofrecognition or reporting of the diseases or that the diseasesare not very common.In the Smith farmed shrimp manuscript, the significant eyelesions that were seen on histopathology were not frequentlyvisible during pond-side evaluation. This supports the afore-mentioned lack of recognition and speaks to the need for slitlamp biomicroscopic evaluations to occur periodically incaptively managed crustaceans.HEXAPODAIntroduction and Natural HistoryThe invertebrate group Hexapoda meaning “six feet” inGreek is a subphylum within Arthropoda that includesinsects, springtails, and bristletails. Class Insecta is an incred-ibly diverse group of organisms with approximately 900,000known species and another estimated 5.5 million species thatare yet to be described (García-Robledo et al. 2020). Insectsinclude the grasshoppers, praying mantises, dragonflies, flies,bees, and beetles among many others. There are a wide arrayof anatomic adaptations and broad sweeping generalizationsof animals in this group should be avoided. This group alsoincludes some of the most well-developed and studiedinvertebrate eyes.Similar to the other arthropods discussed in this chapter(chelicerates and crustaceans), this group also has an exo-skeleton cuticle. The body is divided into three sections: thehead, a three-segmented thorax, and an abdomen. Each tho-racic segment has a pair of legs for a total of 6 limbs (charac-teristic of this group) and wings may also be present.Clinical TechniquesSafety hazards differ between insect groups and can includevenomous stings, bites, or irritating secretions and “hairs”;use of appropriate protective equipment is recommended.Careful observation of the behavior of both individuals andthe colony as a whole can often provide insight and cluesabout the health of an insect group that may be overlooked ifonly close examination is used. Insects may be placed intoclear containers for visual inspection. Magnification can beuseful for evaluation of small individuals. For managedinsect colonies, it may be appropriate to select a subset of26 J. L. Gjeltema et al.animals for diagnostic testing including histopathology, cyto-logic evaluation of external samples, microscopic evaluationof homogenized samples, PCR for suspected pathogens, orother diagnostic tests. Hemolymph may be collected fromlarger individuals, although interpretationof results can bechallenging.Anesthetic agents used in terrestrial insects includeisoflurane gas, sevoflurane gas, and carbon dioxide whilebenzocaine and tricaine methanesulfonate baths have beenreported for anesthesia of aquatic insects (Lewbart 2011).These are generally considered safe and effective for mostinsects, although monitoring physiologic parameters andanesthetic depth has typically been based on crude observa-tional parameters such as patient movement. In many cases, itcan be challenging to discern a state of deep anesthesia fromdeath, particularly in smaller specimens.Although some surgical interventions are described, mosthave been performed for research purposes rather than forclinical treatment of animals. Repairs to damaged exoskele-ton can be attempted with cyanoacrylate, adhesive patches,and other materials. Many species of insects have the abilityto regenerate lost limbs if immature. Pharmacologic treat-ment of insects can be pursued, however, little informationabout appropriate routes, safety, or efficacy are available inthe literature. Delivery routes include oral administration viafood, topical application, nebulization, or in some cases viaintracoelomic injection (Lewbart 2011). It is important tonote that some insects, like honeybees, may be consideredimportant food animals and regulatory requirements must bemet when prescribing medications.Ophthalmologic Anatomy and PhysiologyMost insects including bees, cockroaches, grasshoppers, anddragonflies have compound eyes similar to those describedfor crustaceans (Fig. 2.16). Although many flying insects andlarval life stages have single-chambered eyes. The appositioncompound eyes include many ommatidia (the functional unitcomposed of an external facet lens at the outer surface of theeye and a rhabdom made up of 8 receptor cells). The facetlens defines the field of view and acceptance angle of light foreach ommatidium. Light received into each ommatidiumbecomes “averaged” by internal reflection and contributes asmall part of a larger erect/non-inverted mosaic image pro-duced by the adjacent contributions from all ommatidium.Resolution is limited by diffraction associated with the smallsize of the lenses that make up the compound eye surface.Sections of larger facet lenses may be present for somespecies to allow for enhanced resolution for a portion of theimage produced. As with other previously discussed groupswith ommatidial eyes, pseudopupils are common amonginsects (Fig. 2.17) (Exner 1988). The pattern formed bypseudopupils varies by species or group and depends on thenatural history of the animal. Regions of higher resolutionvision in insect eyes, produced either by larger lens facets orsmaller inter-ommatidial angles, occur in areas of the com-pound eye that serve the evolutionary ends of survival andreproduction.Some insects including male glowworms, fireflies, andbeetles have a multichambered eye structure called therefracting superposition compound eye. Rather than havingfacet lenses as described for the compound apposition eye,this type of eye has optical elements close to or attached tothe cornea that act as inverters. The inverter is formed by alens-cylinder with a gradient refractive index (Exner 1988).The cylinder is twice as long as the distance to the first focusallowing light to emerge from the same rather than oppositeaxis of the lens. There is a wide clear zone between theoptical elements and retina that allows convergence of raysas shown in Fig. 2.18. This leads to a non-inverted focusedimage with high spatial resolution.Moths also frequently have superposition eyes composedof a cornea and a crystalline cone that is loosely attached tothe cornea, which together forms the optical elements neces-sary for refracting superposition optics. These eyes can beuseful for night vision as they provide a broad area forcollecting light that contributes to a bright image (MichaelF. Land 2018). Pigment between cones can migrate to reducelight reaching the retina under high luminance conditions insome species. Butterflies have eyes with afocal appositionoptics that adapted from refracting superposition eyes ofmoths. Each ommatidium has two-lens-cylinder optics thatreduces a beam to the size of the rhabdom, which directlycontacts the optical elements (Michael F. Land 2018).Most flying insects also have three small single-chambered lens eyes on top of the head called dorsal ocellithat function to detect the horizon (Fig. 2.19). These aresomewhat similar in organization, structure, and function tothe eyes of spiders and crustaceans.Clinical ProblemsClinical problems in insects are often a result of inappropriatehusbandry and careful review of temperature, humidity, andsubstrate along with other environmental conditions is key topreventing disease. Inappropriate husbandry and preventivehealth protocols (like quarantine measures) can lead tostressors that impact immune function, difficulty molting, orincreased exposure to and susceptibility to pathogens includ-ing fungi, viruses, parasites, and bacteria. For closedpopulations with uncontrolled breeding, genetic defectsmay also arise. Most described clinical problems in insectsfocus on conditions that affect overall mortality with verylittle information provided about ophthalmological disease,2 Ophthalmology of Invertebrates 27specifically. Trauma, of course, is also an always possiblesource of ocular pathology. Globe indentation/collapse doesoccur, but the cause and significance are unclear at this time(Fig. 2.20).CHELICERATAIntroduction and Natural HistoryChelicerata is a class within the phylum of Arthropoda.Although phylogenic relationships continue to be elucidated,chelicerates typically include the spiders, scorpions, seaspiders, and horseshoe crabs. These animals are often keptin zoological or aquarium collections for exhibition purposes.They are also used for medical or research applications. Forexample, horseshoe crab (Limulus spp.) hemolymph is thesource of Limulus amebocyte lysate used in assays for endo-toxin detection for quality control of pharmaceutical produc-tion and is also used to diagnose cases of suspected sepsis inhumans (Tinker-Kulberg et al. 2020). Recent research ofscorpion and spider venoms has also provided insight intonovel avenues of therapeutic treatments for various diseasesincluding diabetes mellitus, pain management, cancer, andautoimmune disorders as well as insecticides used for agri-culture (Robinson and Safavi-Hemami 2017) (Peptide Ther-apeutics from Venom n.d.). This makes them desirable forresearch and commercial applications.Chelicerates have segmented bodies, jointed limbs, and achitinous exoskeleton cuticle. Appendages anterior to the oralcavity are the common distinguishing feature of chelicerates.These appendages likely have evolutionary origins asantennae and may be present in a variety of forms includingfangs or pincers. Although not visibly distinguishable in allFig. 2.16 Examples of compound eyes possessed by insects: (a) Amale Mayfly Ephemeroptera, (b) Black horse fly Tabanus atratus, (c)Green-eyed crane fly Tipula bicornis, (d) Fly compound eye, 100xmagnification. (a, d)—Used with permission from Cornel Constantin,Shutterstock.com. (b, c)—Used with permission from Mihai_Andritoiu,Shutterstock.com28 J. L. Gjeltema et al.http://shutterstock.comhttp://shutterstock.comspecies, the body of animals in this group is divided into twomajor sections: the prosoma or “cephalothorax” (anteriorsegment) and opisthosoma or “abdomen” (posterior seg-ment). There is an open or semi-open circulatory systemwith a tubular heart located at the dorsal opisthosoma thatmediates hemolymph flow between body segments andsections. Gas exchange occurs either via gills in aquaticspecies or via book lungs in terrestrial species. NitrogenousFig. 2.17 Pseudopupils formed by regions of smaller inter-ommatidialangles of compound eyes in an Australian walking stick Extatosomatiaratum. Courtesy of Bret A. MooreFig. 2.18 Photomicrograph of the eye of a whirligig beetledemonstrating a refracting superposition compound eye structure thatincludes a cylinder lens and wide clear zone between optical elementsand retina. Stain ¼ Hematoxylin & Eosin. Courtesy of the ComparativeOcular Pathology Laboratory of Wisconsin2 Ophthalmology of Invertebrates 29Fig. 2.19 Three single-chambered dorsal ocelli that function to detectthe horizon in many flying insects are located at the head between thetwo larger multi-chambered compound eyes of this (a) Yellow jacketVespula sp. and (b) Giant wasp Sphecius speciosus. (c) Histologicsection of a wasp head showing two of the three single-chambereddorsal ocelli positioned between the eyes on either side. (a)—Courtesyof Bret A. Moore. (b)—Used with permission from Cornel Constantin,Shutterstock.com. (c)—Courtesy of the Comparative Ocular PathologyLaboratory of WisconsinFig. 2.20 Collapse of a compound eye in (a) a dragonfly, and (b) a flyspecies. The cause is suspected to be related to trauma, but is not knownfor certain why it occurs. (a)—Used with permission from Opayaza12,Shutterstock.com. (b)—Used with permission from Razvan CornelConstantin—Alamy Stock Photo30 J. L. Gjeltema et al.http://shutterstock.comhttp://shutterstock.comwaste is removed via nephridia or Malpighian tubules andexcreted via the gut. Paired nerve ganglia are associated witheach body segment and in some species can aggregate toform a rudimentary brain. In addition to vision, varioussensory adaptations are present including specialized nervereceptors for sensing vibrations, air or water currents, exo-skeleton strain, and detecting chemicals in the environment.Some spiders are even able to detect prey using small hair-like extensions of the exoskeleton to sense air currents.Growth requires periodic molting of the exoskeleton cuti-cle and can leave the animal vulnerable for several days untilthe new flexible exoskeleton hardens. Tarantulas will posi-tion themselves in dorsal recumbency when preparing to moltand should not be disturbed during this time due to potentialdamage that may be caused to the new exoskeleton. Somespecies may autotomize (voluntarily release) limbs or poste-rior body segments if stressed. While limbs may re-grow insome species with subsequent molts, loss of a “tail” in ascorpion is a terminal condition due to extension of thetube-like gastrointestinal tract to the tip of the “tail,” wherethe vent is located.HandlingHandling animals in this group can be a challenge and thereare several important adaptations for defense that can pose asafety hazard to a handler. Spiders and scorpions have potentvenoms that can be delivered via fangs or, in the case ofscorpions, via stingers at the tip of the most posterior bodysegment (the telson). Envenomation can cause reactionsranging from unpleasant to fatal (Isbister and Bawaskar2014). In addition to envenomation, scorpions and horseshoecrabs both have pincers that can potentially grasp, poke, cut,and crush with precision. Tarantulas pose their own ophthal-mologic hazard to the unsuspecting ophthalmologist withapproximately 90% of “New World” Theraphosid (tarantula)species having specialized barbed hair-like setae on the limbsor abdomen that can be released defensively by the spider(Bertani and Guadanucci 2013). These may embed andmigrate in skin or eyes, causing irritation or even permanenttissue damage (Reed et al. 2016) (Choi and Rauf 2003)(Sheth et al. 2009). Use of gloves, long-sleeves, goggles,and appropriate post-handling hygiene measures isrecommended even for otherwise docile animals that posefew other safety risks. Due to the variability in hazards posed,it is important to know what species you are working withand understand the precautions that are needed prior tobeginning an exam.The movement of these animals can be sudden, explosive,and unpredictable. Their open circulatory system and rigidexoskeleton make trauma from falls a potentially fatal condi-tion as exoskeleton fractures can lead to hemorrhage,infections, or later molting difficulties that can lead tomortality. Use of a clear container is often an effectivemethod for conducting an initial visual assessment of smalleranimals and use of an experienced handler is stronglyrecommended during manual restraint. Large docile spidersthat do not pose a significant envenomation hazard can some-times be cupped or guided to stand in the palm supporting theweight of both the prosoma and the opisthosoma. Docile andlow-risk species of scorpions can be lifted by gently graspingthe “tail” tip with forceps being careful not to damage orcrush the exoskeleton. Horseshoe crabs can be lifted by thesides of the carapace. Species known to release limbs or tailshould not be restrained by or picked up using theseappendages due to risk of autotomy.When using manual restraint, handling the animal at closeproximity to the working surface or a containment enclosureis recommended to limit risks to the animal. In some cases,due to animal temperament or potential safety hazards, it maynot be appropriate to manually restrain some species. In caseswhere manual restraint is not feasible or safe, chemicalrestraint may be the most appropriate method. A variety ofanesthetic methods have been described for Chelicerates(Gjeltema et al. 2014) (Dombrowski et al. 2013) (Archibaldet al. 2019) (Zachariah et al. 2014). Terrestrial species canoften be effectively immobilized using gas anesthesia deliv-ered via chamber induction and aquatic species can besubmerged in anesthetic baths, such as tricainemethanesulfonate.A variety of clinical techniques have been described forchelicerates. Hemolymph collection for culture, cytology,chemistry, or other diagnostics, may be obtained from thedorsal opisthosoma at midline in the location of the heart forlarge spiders, at the dorsal midline hinge-like arthrodial junc-tion between the prosoma and opisthosoma in horseshoecrabs, and dorsolaterally between the third to fifth segmentsof the opisthosoma (called tergites) in scorpions (Lewbart2011). These sites may also be used for injections ofmedications, fluids, or even hemolymph transfusions, as hasbeen described in tarantulas (Visigalli 2004). Informationregarding safe and effective dosages of medications as thera-peutic options are largely unavailable, requiring relianceupon extrapolation (possibly inappropriately) from reptiliandosages, experimental research studies using invertebratemodels, or anecdotal reports (Gjeltema et al. 2014).Ophthalmologic Anatomy and PhysiologyChelicerates may have combinations of compound eyes(horseshoe crabs) and/or clusters of single-chambered ocelli(spiders and scorpions). The specific number and arrange-ment of the eyes may be used for taxonomic differentiation insome groups. Because of the visual acuity required for hunt-ing, the ocular anatomy and vision of some species, such asjumping spiders (Salticidae spp.), are well-developed and2 Ophthalmology of Invertebrates 31have been described in significant detail. The eyes of horse-shoe crabs (Limulus spp.) have also attracted much study dueto their prominence as a model animal in neurology research.Spiders typically have four pairs of single-chambered eyesgenerally referred to by their positions on the animal’s pro-soma (Fig. 2.21). The anterior median eyes are considered the“principal” eyes with all others (posterior median, anteriorlateral, and posterior lateral) being considered “secondary”eyes. Some families of spiders only have 6 eyes, lacking thepair of principal eyes while retaining all secondary pairs(Barth 2002). Similar to spiders, scorpions have a prominentpair of “median” single-chambered eyes located at the centerof the dorsal prosoma and smaller “lateral” eyes (2–4 pairs)generallylocated at the anterolateral edge of the prosoma.“Primary” and “median” eyes are similar to crustacean nau-plius eyes and the ocelli of flying insects and differ signifi-cantly in structure and function from the spider’s“secondary” and the scorpion’s “lateral” eyes. The horseshoecrab (Limulus spp.) has 10 pairs of eyes including two lateralcompound eyes, two rudimentary lateral eyes, two medianeyes, two ventral eyes, one endoparietal eye, and aphotoreceptor array at the “tail” (telson). There is someevidence to suggest that the different eye types of spidersdeveloped from an ancestral species that had both single-chambered and compound eyes. The primary ocelli of spidersmay have evolved and developed from the ancestral single-chambered eye with each of the secondary eyes evolvingfrom gradual separation of individual chambers of the ances-tral compound eye (Barth 2002).The horseshoe crab’s lateral compound eyes are similar instructure to the superposition refracting compound eyesdescribed for other arthropods discussed in previous sectionsof this chapter. The rudimentary “eyes” of the horseshoe crabincluding ventral, lateral rudimentary, endoparietal, and thephotoreceptor array are less organized masses of photorecep-tor cells that serve to detect lunar cycles and circadianrhythms (Harzsch et al. 2006).All of the spider and scorpion eyes as well as the twomedian eyes of the horseshoe crab are single-chamberedocelli with cuticular lenses (Jones et al. 1971) as shown inFig. 2.22 b. The principal eye of spiders has a conical tubularshape. The lens is fixed in place, however, there are threeFig. 2.21 The four pairs of single-chambered eyes of spiders, showingvariation of the position and size of the paired primary and secondarysingle-chambered lens eyes (not all visible in these images). (a) A meshweb weaver species, Dictyna brevitarsa, (b) a male Woodlouse hunterspider Dysdera crocata, (c) an orb weaver spider species, Plotysillepidus, and (d) a Thomisidae Crab spider Xysticus sp. (a, b)—Usedwith permission from Mihai_Andritoiu, Shutterstock.com. (c)—Usedwith permission from Wanchat M. Shutterstock.com. (d)—Used withpermission from Ireneusz Waledzik, Shutterstock.com32 J. L. Gjeltema et al.http://shutterstock.comhttp://shutterstock.comhttp://shutterstock.compairs of muscles that are positioned around the eye thatcontrol movement in horizontal, vertical, and rotationalplanes (Williams and MeIntyre 1980). These muscles allowthe spider to move its retina to focus on an image. The lens ofspiders is biconvex with the inner lens surface having a largerradius of curvature than the outer lens surface. Lenses of thelateral eyes of scorpions may be flatter and do not producefocused images (Meyer-Rochow 1987). There is a cellularvitreous body present between the lens and retina for allspider eyes, although the vitreous body may be lacking inthe lateral eyes of scorpions (Barth 2002; Jackson andHarland 2009).The retina ranges in its complexity of layering and types ofphotoreceptors by species. Most spider rhabdoms typicallyhave one to two rhabdomeres composed of microvilli that arepositioned on opposite sides of the photoreceptor cell. Theprincipal eyes of spiders lack a tapetum and the retina iseverted with the rhabdomeres pointed toward the incidentlight. Fovea may be present in the principal eyes but are notpresent in secondary eyes. In some jumping spiders, aV-shaped “pit” with a refracting interface allows fortelephoto magnification and higher resolution than is possiblefor the corneal lens alone (Fig. 2.22) (Jackson and Harland2009; Williams and MeIntyre 1980). Together the layers anddifferent photoreceptor types take advantage of chromaticaberration for discernment of up to 4 colors including ultra-violet light (Barth 2002; Lazareva et al. 2012; Williams andMeIntyre 1980). The retinas of secondary spider eyes areinverted, with rhabdomeres pointing away from the incidentlight. A tapetum is formed by reflective crystals locatedbetween photoreceptor cells in the retina. Secondary eyeshave no fovea and less layering than principal eyes, and theretina can be directly observed with the use of an ophthalmo-scope. Photoreceptor microvilli of the rhabdomeres in night-active spiders may change dramatically between theconditions of day and night, with dramatic expansion ofmicrovillar membranes to facilitate vision in low light nightconditions (Barth 2002).Although the resolution for principal eyes of jumpingspiders is high and comparable to some birds and mammals,it does not exceed that of humans, due to lower receptor celldensity. For example, the eyes of a jumping spider (Portiafinbriata), has an inter-receptor angle of 2.4 minutes of arccompared to 0.42 in humans (Williams and MeIntyre 1980).Although the resolution of secondary eyes in spiders andlateral eyes in scorpions is generally considered poor, itsignificantly expands the overall field of view for spiderswhen the fields of all eyes are combined.Clinical ProblemsAs with other groups of invertebrates, clinical problems ofchelicerates are often a result of inappropriate husbandry orhandling and careful review of temperature, water quality,humidity, and substrate along with other environmentalconditions is key to preventing disease. Trauma or diseaseaffecting the exoskeleton or cuticle is common and can leadto infection, dysecdysis (difficulty molting), dehydration,parasitism, or functional deficits; and have the potential tosignificantly affect ophthalmologic health as well.Other Invertebrate GroupsCnidariaThis large phylum includes the comb jellies (Ctenophores),Hydrozoans (hydras, fire coral, Portuguese Man-O-War),Scyphozoans (jellyfishes), and Anthozoans (stony corals,Fig. 2.22 (a) Macro photograph and (b) photomicrograph of the single-chambered eyes of a jumping spider Salticidae showing the conicaltubular primary eyes with a V-shaped “pit” for telephoto magnification(arrowhead). Stain (b) ¼ Hematoxylin & Eosin. (a)—Used with permis-sion from Mihai_Andritoiu, Shutterstock.com. (b)—Courtesy of theComparative Ocular Pathology Laboratory of Wisconsin2 Ophthalmology of Invertebrates 33http://shutterstock.comsoft corals, and sea anemones). This is a highly economicallyimportant group for environmental monitoring, public andprivate display, research, and tourism. Jellyfish exhibits arenow some of the most popular displays in public aquariums,upscale restaurants, and even in private homes throughout theworld. Coral reefs collectively are one of the most beautiful,diverse, and fragile ecosystems on the planet. Public andprivate reef aquariums are one of the largest areas of growthin the aquarium industry. Investigations on the diseases ofcorals are some of the most active areas of research for anyaquatic animal group.Only some of the scyphozoans (jellies) have rudimentaryeyes, called ocelli, which are no more than pigmentedphotoreceptors and are usually associated with the multisen-sory rhopalium (Nakanishi et al. 2009). Figure 2.23 illustratesthe development and anatomy of the rhopalium in Aureliasp. Rarely, the polyp stage of a scyphozoan may have ocelli,as is the case with Stylocoronella riedli (Blumer et al. 1995).TurbellariansFor many decades and until about 2010 the turbellarians(free-living flatworms) were included in the phylumPlatyhelminthes along with parasitic forms like cestodes,digenea, and monogenea (Ruppert et al. 2004). A surge inmolecular research has reorganized the group due to strongevidence that many members are paraphyletic (not allmembers of the taxon share a common ancestor) (Littlewood2008). Modern genomic techniques and data indicate thatturbellarians should be in the phylum Xenacoelomorpha(Philippe et al. 2011; Tyler et al. 2006-2016).Many aquatic and terrestrial species of free-livingflatworms have photoreceptors, and while turbellariansevolved in water, having somevision likely contributed totheir ability to colonize land (Sluys 2019). Despite many taxahaving photoreceptors that could be termed eyes, at this pointwe do not have a clinical foothold for this taxon with regardto veterinary ophthalmology.AnnelidaThe annelids are a large (over 20,000 species), diverse groupof segmented worm-like animals that are divided into threemain classes: Polychaeta, Clitellata (earthworms andleeches), and Sipuncula (formerly its own phylum andknown colloquially as the peanut worms). All arecharacterized by regular segmentation of the body and thissegmentation likely evolved as a means of burrowing viaperistaltic contractions (Ruppert et al. 2004). Annelids pos-sess a segmented coelomic cavity that is divided by regularsepta. The circulatory, excretory, and nervous systems arealso segmented. Segmented setae occur in nearly all membersFig. 2.23 Rhopalium development and anatomy in the scyphozoan (jelly), Aurelia sp. Used with permission from “Nakanishi et al. (2009).Development of the rhopalial nervous system in Aurelia sp. 1 (Cnidaria, Scyphozoa). Development Genes and Evolution, 219(6), 301–317”34 J. L. Gjeltema et al.of the phylum and the animal is covered by a cuticle. Thestraight gut has an anterior mouth and a posterior anus(Ruppert et al. 2004).In 2005, the genome of Platynereis dumerlii, a free-livingpolychaete, revealed interesting and enlightening informationon the annelids’ place in the overall taxonomic scheme of theworld’s animals (Raible et al. 2005). Based on the geneticfindings from this study, annelids are more closely related toHomo sapiens than they are to some other invertebrates,including insects and nematodes.The polychaetes are a morphologically and physiologi-cally varied group of over 8000 species that belong to86 families (Ruppert et al. 2004). Nearly all are marine, andsizes vary from less than a millimeter to a meter in length.They occupy a variety of aquatic habitats, and many burrowor build tubes in or upon marine sediments and substrates. Ofall the annelids, polychaetes have the most developed eyesand other sensory structures. The sensory prostomium, whichtypically contains antennae, eyes, and tentacles, is locatedabove and anterior to the oral opening. Purschke et al. (2006)provide a detailed and interesting review of eyes andphotoreceptors of annelids (Fig. 2.24) (Günter Purschkeet al. 2006). There is a lot of interest in the evolution of theeye in different invertebrate and vertebrate taxa, and while afascinating topic, is beyond the scope of this review. Eyesand vision probably evolved independently and convergentlyFig. 2.24 Transmission electron microscopy of polychaete annelideyes illustrating the different types of photoreceptors. Used with per-mission from, “Purschke, Günter, Arendt, D., Hausen, H., & Müller,M. C. (2006). Photoreceptor cells and eyes in Annelida. ArthropodStructure & Development, 35(4), 211–230”2 Ophthalmology of Invertebrates 35in many groups, although, it is likely that metazoans share acommon and ancient photoreceptor cell type (GünterPurschke et al. 2006).Annelids possess three different types of photoreceptorcells (all illustrated in Fig. 2.24). Rhabodomeric cells utilizemicrovillar photoreceptive membranes (Günter Purschkeet al. 2006). The ciliary cell type possesses cilia that projectinto an extracellular space (Günter Purschke et al. 2006). Thethird type of photoreceptor is termed a phaosome (Fig. 2.25).Phaosomes are intracellular vacuoles that contain photore-ceptive elements. These cells are uncommon in polychaetesbut represent the primary photoreceptor for the clitellatids(earthworms and leeches) (GÜNTER Purschke et al. 2014;Günter Purschke et al. 2006).EchinodermsThis diverse and interesting group of exclusively marineanimals includes the sea stars (asteroids), brittle stars, seacucumbers, sea urchins, sea biscuits, and crinoids (featherstars). Many are commonly displayed in aquaria, used inresearch, and occasionally consumed by humans (sea urchingonads and sea cucumbers). While it appears all members ofthe phylum have some means of photodetection, asteroids(sea stars) are the only class that has well-developed eyes,and typically associated with the terminal arm (Ruppert et al.2004) (Lowe et al. 2018). Photodetection and response tolight are important to echinoderms even if forming images isnot. 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Series B, Biological Sciencesby a library of high-quality photographic images and informative illustrations.Importantly, knowledge gaps are identified which will hopefully stimulate investigations bycurrent and future comparative ophthalmologists.The editors are to be applauded for bringing this daunting project to fruition. The tragic lossof one of the editors, Dr. Gil Ben-Shlomo, is felt throughout the profession, but I feel Gil wouldbe truly pleased in seeing the quality of the product his hard work was central to completing.I note that this is the first edition of what I feel is likely to become a cornerstone reference forcomparative ophthalmology. I am very much looking forward to its continued evolutionthrough subsequent editions.Department of Ophthalmology and Vision Science,Department of Veterinary Surgical and Radiological Sciences,Schools of Medicine and Veterinary Medicine,University of CaliforniaDavis, CA, USAChristopher J. MurphyviiPrefaceNo matter how small or large, the differences between one animal and the next display all thesplendor and exulting power of nature. Biologist David Barash once said that it is an innatebehavior of us humans to be fascinated with animals, often viewing them as either straight ordistorted reflections of ourselves. Our captivation of the animal kingdom has included acuriosity of how animals see, a topic that also has largely been impacted by our personalexperiences with the visual perception of our shared world. In fact, for nearly 300 years, thevertebrate eye has been a structure of scientific fascination. Early work provided both insightand foresight into the questions needing to be asked, and those answered have shaped ourcurrent understanding of the vertebrate eye. Gordon L. Walls himself said, as he introduced TheVertebrate Eye and Its Adaptive Radiations in 1942, that,If the comparative ophthalmologists of the world should ever hold a convention, the first resolution theywould pass would say: ‘Everything in the vertebrate eye means something.’ Except for the brain, there is noother organ in the body of which that can be said. . .Man can make optical instruments only from suchmaterials as brass and glass. Nature has succeeded with only such things as leather and water and jelly; butthe resulting instrument is so delicately balanced that it will tolerate no tampering.How right he was, as we continue to learn that we still know relatively very little. Thisstatement was made just a few short decades from the official conception of our college, theAmerican College of Veterinary Ophthalmology, which as of November 2019 celebrated its50th Anniversary in beautiful Maui, Hawaii, and paid tribute to those who initiated itsdevelopment (Samuel Vainisi, Roy Bellhorn, Seth Koch, Charles Martin, Milt Wyman,Stephen Bistner, William Magrane, Kirk Gelatt, Craig Fischer, Gustavo Aguirre, and LionelRubin). Similarly, our Brazilian (Est. 1987) and European (Est. 1991) Colleges of VeterinaryOphthalmology followed years later.Over the past 50 years, we have advanced the field of comparative ophthalmology at a nearexponential rate. Establishment of a mainstay text for canine and feline ophthalmology wasintroduced in 1981 by Kirk N. Gelatt, a book that is currently in its sixth edition. A mainstaytext of equine ophthalmology has been developed and is now in its third edition thanks to BrianGilger’s dedication, completing the triad of our most commonly treated companion animals.However, as major advances are made with a particular focus on the treatment and preventionof ophthalmic disease in our animal companions, the wonder and beauty of the enormousdiversity that is the vertebrate eye can be lost. In many regards, a major gap not yet embodiedwithin our progression as a college is the true comparative nature of our profession. Even in theface of much scientific progress, much of the knowledge to date in wild and exotic animalophthalmology has depended upon extrapolation from domestic animal ophthalmology. Theocular anatomy, physiology, and most common ophthalmic diseases in many wild and exoticanimal species are still largely unknown to veterinarians.Despite our utmost desire to improve care for the eyes of our domestic animal companions,we are truly privileged to be able to work with all the species of the Earth, from the smallestinsect to the largest whale. In honor of the beauty of the vertebrate eye and perhaps its mostremarkable attribute—its unimaginable and inspiring diversity—it is with excitement andenthusiasm that we are able to present to you this book, Wild and Exotic AnimalixOphthalmology. Our goals have been twofold: (1) to provide a comprehensive yet clinicallyfocused text to guide ophthalmologists and exotic animal and zoological practitioners and (2) toestablish a collection of the achievements we have made thus far and, more importantly, aperspective on what achievements we have yet to make in the field of exotic animalophthalmology.To accomplish our first goal, a major hurdle of such a text is to organize both clinical andtaxonomic aspects in harmony. Before getting into details about vision, eye diseases, andtreatment, we introduce each taxonomic class, offering general information on biology, physi-ology, husbandry, nutrition, and sometimes even common systemic diseases. Because animalsare typically grouped by phylogenetic relatedness, understanding taxonomy will assist veteri-nary ophthalmologists to better categorize our patients, facilitating possible extrapolations ofknowledge already constructed in domestic animals or in more familiar exotic species.This two-volume book begins with an introduction to the origins of photoreception (Chap. 1)and its beginnings in the invertebrates (Chap. 2) and the fishes (Chaps. 3, 4, 5) in Part I. Here,we are introduced to the vertebrate eye, of which the cyclostomata, the jawless fish, provides aview of what perhaps is the earliest of the vertebrate visual systems. The complexity andophthalmic diversity rapidly grows as we move onto land and discuss ophthalmology of theAmphibia in Part II (Chaps. 6 and 7) and Reptilia in Part III (Chaps. 8, 9, 10, 11, 12, 13, 14, and15). The Avians (Chaps. 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25) are represented strongly byour clinically prominent groups, the psittacines (Chap. 17), the raptors (Chap. 20), and theGalloanserae (Chap. 24). In addition to Chap. 16: Introduction to Avian Ophthalmology, thesethree chapters provide a framework for practicing ophthalmology in birds, and specificdifferences among other avian groups are highlighted within their respective chapters.Approaching the Mammalia (Volume 2) in a similar way would be foolish, as the diversityfrom a clinical perspective far exceeds that of the Avians (at least to our current understanding).From the vestigial subterranean eyes of moles, to the reptilian-like eye of the echidna, to the4-kilogram eye of a blue whale, introducing the features of the mammalian eye is bestaccomplished within each chapter. We end with several Appendices for easy reference.With our second goal of this book being to arouse memories of old when working withdifferent species, and to stimulate foresight on what could be, we have spent time reflecting onthe progression and meaning of our profession. “Let there be light” is an English translation ofthe Hebrew רֹואיִהְי (yehi ‘or), found in Genesis 1:3 of the Torah. Light has been the subject ofwonder since the dawn of humankind. The word enlightened comes from the Latin prefix enmeaning “in, into” and the word lux meaning “light.” Combined, “into the light” describes theentire basis of our field of veterinary ophthalmology. Light notably possesses twocharacteristics: it is wave-like, interfering in the same way that water ripples cross each other,but it is also particle-like, carrying its energy in discrete bundles known as photons (or quanta).Light stimulus has an intensity, a direction, a spectrum (color),245(718):1–18Zachariah, T. T., Mitchell, M. A., Watson, M. K., Clark-Price, S. C., &McMichael, M. A. (2014, May 27). Effects of sevoflurane anesthesiaon righting reflex and hemolymph gas analysis variables for Chileanrose tarantulas (Grammostola rosea) (1931 North Meacham Road,Suite 100, Schaumburg, IL 60173–4360 USA 847–925-8070847–925-1329 avmajournals@avma.org) [Research-article]. doi:https://doi.org/10.2460/Ajvr.75.6.521; American Veterinary Medi-cal Association 1931 North Meacham Road, Suite 100, Schaumburg,IL 60173–4360 USA 847–925-8070 847–925-1329avmajournals@avma.org. doi:https://doi.org/10.2460/ajvr.75.6.521Zieger MV, Meyer-Rochow VB (2008) Understanding the cephalic eyesof pulmonate gastropods: a review. Am Malacol Bull 26(1/2):47–662 Ophthalmology of Invertebrates 39https://doi.org/10.1038/288578a0https://doi.org/10.1038/288578a0https://doi.org/10.1016/j.aqrep.2020.100524https://doi.org/10.1016/j.aqrep.2020.100524https://doi.org/10.2460/Ajvr.75.6.521https://doi.org/10.2460/ajvr.75.6.521Ophthalmology of Agnatha: Lampreys and Hagfish 3David L. Williams# Chrisoula SkouritakisD. L. Williams (*)Department of Veterinary Medicine, University of Cambridge,Cambridge, UKe-mail: dlw33@cam.ac.uk# Springer Nature Switzerland AG 2022F. Montiani-Ferreira et al. (eds.), Wild and Exotic Animal Ophthalmology, https://doi.org/10.1007/978-3-030-71302-7_341http://crossmark.crossref.org/dialog/?doi=10.1007/978-3-030-71302-7_3&domain=pdfmailto:dlw33@cam.ac.ukhttps://doi.org/10.1007/978-3-030-71302-7_3#DOIIntroductionClearly, the earliest eyes existed well before the developmentof the vertebrate body, but it is the jawless fish, the Agnathi,which provide us with the best approximation of whatadvances and changes occurred in the eye at this inverte-brate-vertebrate transition. I say approximation, as the eyes ofmodern-day lampreys and hagfish may not mirror exactly thesituation 250 million years ago, given that the current ocularmorphology may represent a degenerative evolution since theeyes of the hagfish being situated now under the pigmentedskin and appear to not have an image-producing visual func-tion but rather they are light sensitive. However, fossil evi-dence points to their ancestors having complex compoundeyes. The current hagfish eye is one that has, it would seem,undergone degeneration from a previously far more func-tional visual system (Fernholm and Holmberg 1975).The Agnathid Jawless FishToday the jawless fish, comprising the hagfish and the lam-prey, are but a small part of the breadth of marine fauna. Yet400 million years ago in the early Paleozoic, they were a keypart of the developing fish family (Evans et al. 2018). Later,armored agnathans the ostracoderms were the precursors ofbony fish and thus to tetrapods of today including humans.The two remaining agnathids extant today, the hagfish andlamprey, are both cyclostomes without a conventional jawbut rather having a circle of horny epidermal structures. Thehagfish, a member of the Myxini, is the only known animalliving today with a cranium but no vertebrae. Some haveconsidered it a degenerate form of a previous vertebratelineage but today most are of the opinion that it representsan animal preceding the evolution of the vertebral column,rather similar to the lancelet Amphioxus. Amphioxus,discussed briefly above, has bare photoreceptors, the Josephcells and Hesse cells, and a single frontal eye (Vopalenskyet al. 2012). This is a pigment cup homologous to the retinalpigment epithelium which expresses the pax 6 gene and thenseveral rows of cells. The first of these are the photoreceptors,flask shaped with long ciliary processes. These cells expressthe opsin c-opsin 1 and two rows of serotonergic neurons,homologous to retinal ganglion cells and which project to thetegmental neuropil, a locomotor control structure.Eyes of the HagfishHagfish, as members of the cyclostome group, are the oldestgroup of living vertebrates showing development of eyes.Although they are in all probability functional light receptors,hagfish eyes are small and lack a lens, extraocular muscles,and the three motor cranial nerves (III, IV, and VI), which arekey in the development of more complex eyes (Fig. 3.1).Hagfish eyespots, when present, can detect light but none canresolve detailed images. Indeed, in the species Myxine andNeomyxine, the eyes are partly covered by the trunk muscu-lature. Paleontological evidence suggests, however, that thehagfish eye as it stands today is not plesiomorphic, that is tosay, representative of an ancestral state, but rather degenera-tive. Fossils from the Carboniferous period demonstratehagfish-like vertebrates with complex eyes. One might askwhat possible evidence there can be of fossil invertebrateeyes, given that they comprise soft tissues without any skele-tal elements which we normally think of when consideringfossils. Yet evaluation of ancestral species from sources suchas the Burgess Shale has over the past decades demonstrateda huge range of invertebrates, the soft tissues which leave adark stain from carbon that turns into mica and silicates.Microscopic evaluation can reveal pigment deposits in areasaround the head that are characteristic of retinal pigmentepithelium deposits, thus demonstrating that complexcamera-style eyes existed in these precambrian animals.Although such evidence is sparse, this tends to suggest thatancestral Myxini possessed complex eyes. Indeed, betweendifferent hagfish species, there are significant differences:Eptatretus species have a hollow eyecup with a vitreouscavity and a neuroretina containing photoreceptors with obvi-ous outer segments and which is contiguous with the mar-ginal epithelium but is without iris or ciliary body. TheMyinehave few degenerate outer segments forming only a fewhundred simple synapses with the axons of the optic nerve.Fig. 3.1 The eye of a hagfish (Myxinidae). Note the simplistic retinalarchitecture and lack of a lens42 D. L. WilliamsTheir eyes are buried beneath muscle layers and there is novisible evidence of their existence on the surface of theanimal. Interestingly this is not to say that these hagfish areinsensitive to light. Skin just behind the tentacles has beenshown to be light sensitive as, perhaps surprisingly, has skinaround the cloaca. The degenerate eyes of these species tellus little about evolution of the eye. The other extant agnathidspecies however, the lamprey, has much more to tell us.Eyes of the LampreyTo understand visual function in the lamprey one must rec-ognize the remarkable life history of these animals. Manymay only know of this primitive fish species through itsconnection with the death of King Henry I who, accordingto his chronicler Henry of Huntingdon (1088–1157) died ‘ofa surfeit of lampreys’ (Hollister 2003). Lacking jaws orpaired fins they do represent an ancestral plesiomorphicstate of vertebrates. Using their circular mouth which givesthe cyclostomes their name, adults are often parasitic,attaching to their prey and feeding off body fluids. The larvaehowever burrow into the sand or mud at the bottom offreshwater streams and feed on algae or detritus for severalyears. Their laterally placed visual organ is merely an eyespotwhich after metamorphosis is covered by pigmented skin(Fig. 3.2a). Note however that the skin over the pinealgland is transparent as the prominent zoologist Youngnoted as far back as 1935 and stimulation of the pineal regionwith light elicits responsive behaviors in larvae where thelateral eyes have been destroyed, showing that the pinealcomplex has photoreceptive function (Young 1935). Fiftyyears later Tamotsa and Morita demonstrated that pinealphotoreceptors are morphologically similar to retinal conesand that electrical responses can be recorded from the pinealcomplex of larvae as small as 2.8 cm in length (Tamotsu andMorita 1986). Further researchhas shown that the pinealcomplex contains two rhodopsin-containing cells, oneinvolving parapinopsin dorsally and lamprey rhodopsin ven-trally. The former respond to ultraviolet light with an absorp-tion maximum at a wavelength of 370nm while the latterresponds to green light (Kawano-Yamashita et al. 2007).The lens of the larval eye, although in contrast to that ofthe hagfish sans lens, does exist but could not act as animage-forming structure even if any light filtered through.At metamorphosis, a dramatic change occurs, and a camera-style eye develops (Fig. 3.2b). The skin around the larvalproto-eye becomes transparent and at the same time the retinadevelops to form the cells of the gnathostome eye; rod andcone photoreceptors, bipolar cells, horizontal and amacrinecells and several different types of retinal ganglion cells. Theanterior part of the lamprey lateral eye is comprised of twoparts, a cutaneous or dermal brille derived from and continu-ous with the skin and the cornea proper, derived from thesclera. The brille or spectacle consists of an outer epithelium,an internal stroma and a second posterior epithelium. Amucoid layer separates the outer spectacle from the trueinner cornea. The anterior surface of this true corneacomprises a single layer of epithelial cells. Beneath this liesthe stroma with lamellae similar to the stroma of highervertebrates and the innermost endothelium again is similarto that of more highly developed genera (Fig. 3.3a, b). DuringFig. 3.2 Histologic section of a (a) larval lamprey eye showing an eye located beneath the dermal layer, and (b) an adult lamprey eye that sincemetamorphosis has reached a typical vertebrate camera-style design3 Ophthalmology of Agnatha: Lampreys and Hagfish 43spawning the spectacle becomes opaque, appearing rather thesame as does the snake spectacle during ecdysis (Fig. 3.3c).The reason for the lamprey spectacle opacification is quitedifferent though. The stroma of the spectacle and cornea isinvaded by leucocytes and collagen proteins break down. Thecornea cannot swell though because of proteinaceous suturesFig. 3.3 The eyes of lamprey. (a)A Pacific lamprey (Lampetratridentata) out of water showingnormal gross appearance. (b) Anormal lamprey eye underwater.(c) A spawning lamprey showingopacity of the spectacle. (a) Usedwith permission from MichaelDurham, Nature Picture Library,Science Photo Library44 D. L. Williamsspanning the stroma in a similar manner to the cornea ofcartilaginous fish.A more concerning condition Lamprey Reddening Syn-drome (Brosnahan et al. 2019) has recently been reported inwhich lampreys in specific rivers in New Zealand have beendocumented with skin reddening along the body but specifi-cally anteriorly sometimes associated with exophthalmos.These findings are possibly caused by an atypical Aeromonassalmonicida infection, although other researchers havesuggested this to be an incidental finding and that the condi-tion is actually caused by blunt trauma.The iris of the lamprey is of simple construction with ananterior epithelial layer contiguous with that of the peripheralposterior cornea, a thin stroma and a heavily pigmentedposterior epithelium. There is no ciliary body (and thus nociliary muscles) in these fish and thus the iris is directlycontinuous with the choroid. Iridal muscles similarly areabsent. The lamprey eye has no suspensory ligament of thelens and the spherical lens is held in place by the iris pressingit against the anterior face of the vitreous. It appears thataccommodation, as much as it occurs, is manifest throughmuscles tautening the spectacle and flattening it.Short and long photoreceptors have been documented inlampreys and generally are considered to equate to rods andcones respectively. These cells are similar in structure, bio-chemistry, and physiology to other vertebrate classes (Fain2020). However, retinal ganglion cells are quite differentfrom other vertebrates, in that their axons travel next to theinner limiting membrane, vitread of all other retinal cellbodies and synapses, followed by convergence at an opticfiber layer between the inner plexiform and inner nuclearlayers rather than forming an optic nerve head (Fain 2020).The electroretinogram of the river lamprey has been recordedand consists of four waves characteristic of a mixed rod andcone retina. Different species of lamprey may have quitevarying photoreceptors depending on the photic environmentin which they live. Even within one species of lampreythough variants living in different habitats can differ substan-tially in their photoreceptive abilities. For instance, the south-ern hemisphere lamprey (Geotria australis) has a retinacomprising a long-wavelength sensitive cone absorbing at610 nm, a medium-wavelength sensitive cone absorbing at515 nm, and a medium-wavelength absorbing at506–500 nm. The downstream migrant which, when fullymetamorphosed swims to the sea to feed parasitically on fishin the bright surface waters, has a yellow photostable pigmentin the myoid region in all three of its photoreceptors. How-ever, the upstream migrant has a transparent elliposome in themedium wavelength cone allowing light of yellowwavelengths to pass through, associated with the more turbidwaters of upstream environments (Collin et al. 2000). Wewill use this one example of how the visual apparatus isadapted to varying environments for the agnithids, but aswill be noted in Chaps. 4 and 5 on cartilaginous fish andteleosts of the wide differences in ocular anatomy and physi-ology depending on the visual environment in which the fishlive is key to our understanding of their optical biology.ReferencesBrosnahan CL, Pande A, Keeling SE et al (2019) Lamprey (Geotriaaustralis; Agnatha) reddening syndrome in Southland rivers,New Zealand 2011–2013: laboratory findings and epidemiology,including the incidental detection of an atypical Aeromonassalmonicida. New Zealand J Marine Freshwater Res 53:416–436Collin SP, Hart NS, Shand J et al (2000) Morphology and spectralabsorption characteristics of retinal photoreceptors in the southernhemisphere lamprey (Geotria australis). Vis Neurosci 20:119–130Evans TM, Janvier P, Docker MF (2018) The evolution of lamprey(Petromyzontida) life history and the origin of metamorphosis. RevFish Biol Fish 28:825–838Fain GL (2020) Lamprey vision: photoreceptors and organization of theretina. Semin Cell Dev Biol 106:5–11Fernholm B, Holmberg K (1975) The eyes in three genera of hagfish(Eptatretus, Paramyxine and Myxine) – a case of degenerative evo-lution. Vision Res 15:253–254Hollister CW (2003) Henry I. Yale University Press, New Haven;London, UK, p 467Kawano-Yamashita E, Terakita A, Koyanagi M et al (2007) Immuno-histochemical characterization of a parapinopsin-containing photo-receptor cell involved in the ultraviolet/green discrimination in thepineal organ of the river lamprey Lethenteron japonicum. J Exp Biol210:3821–3829Tamotsu S, Morita Y (1986) Photoreception in pineal organs of larvaland adult lampreys, Lampetra japonica. J Comp Physiol A 159:1–5Vopalensky P, Pergner J, Liegertova M et al (2012) Molecular analysisof the amphioxus frontal eye unravels the evolutionary origin of theretina and pigment cells of the vertebrate eye. Proc Natl Acad Sci109:15383–15388Young JZ (1935) The photoreceptors of lampreys: II. The functions ofthe pineal complex. J Exp Biol 12:254–2703 Ophthalmology of Agnatha: Lampreys and Hagfish 45Ophthalmology of Cartilaginous Fish: Skates, Rays,and Sharks 4David WilliamsD. Williams (*)Department of Veterinary Medicine, University of Cambridge,Cambridge, UKe-mail: dlw33@cam.ac.uk# Chrisoula Skouritakis# Springer Nature Switzerland AG 2022F. Montiani-Ferreira et al. (eds.), Wild and Exotic Animal Ophthalmology, https://doi.org/10.1007/978-3-030-71302-7_447http://crossmark.crossref.org/dialog/?doi=10.1007/978-3-030-71302-7_4&domain=pdfmailto:dlw33@cam.ac.ukhttps://doi.org/10.1007/978-3-030-71302-7_4#DOIIntroductionThe cartilaginous fish or Chondrichthyes are a large andsuccessful group of aquatic organisms, comprising theElasmobranchs, modern sharks, skates and rays (96% ofexisting species) and the Holocephali, chimeras and elephantfish making up the remaining 4%. These fish have a longevolutionary history with members of the lineage being pres-ent in the fossil record 450 million years ago (Sansom et al.1996) and over that time the fish have evolved to occupy awide range of varying ecological habitats. To cope withsubstantially divergent environments, they possess a sophis-ticated battery of sensory systems with olfaction as an excep-tionally sensitive arm of their interaction with theirenvironment. Indeed, this has led some in the past to termthem ‘swimming noses’ (Aronson 1963). Investigation oftheir sense of smell has led to a smaller degree of attentionbeing paid to their vision and ophthalmic anatomy and phys-iology with early investigators such as Walls (1942) andRochon-Duvigneaud (1943) suggesting that their retina waspopulated only by rods rendering the fish scotopic in theirvisual behaviour with poor visual acuity and lacking colourvision. Gruber’s discovery in 1963 that the retina of thelemon shark Negaprion brevirostris possessed rods andcones opened a new field of study in chondrichthic visionand now we know that there are shark species with a highretinal cone population (Gruber and Cohen 1978) and that itis only deep-sea species which have retinae populated solelyby rods (Bozzano et al. 2001). In fact, the visual system ofsharks of the deep (etmopterid and dalatiid species) hasdeveloped numerous strategies for photon capture in a verydim environment, including semicircular tapeta and aphakicgaps not previously shown to exist in elasmobranchs (Claeset al. 2014). Work by Collin’s group more recently has led toa much deeper understanding of the eye in cartilaginous fishand the role of vision in their behaviour (Collin 2018).In this chapter, we will review the eye of these cartilagi-nous fish from an anatomical perspective to show the adapta-tion of various parts of the eye to their external environmentand internal behaviour mechanisms, all of which encouragefuture progress in clinical ophthalmology. Interested readersare directed to the publications particularly from Collin’sgroup upon which much of this review is based. Althoughsparse, when available interjection of clinical ophthalmicinformation and data will be provided.Globe and OrbitAs with most vertebrates, the shark eye is ellipsoid, although,in some species with dorsoventrally flattened heads such asthe Sphyrimid hammerhead sharks, the eye is greatlyelongated rostrocaudally (Muriana et al. 2017). In a terrestrialvertebrate, this would result in defective vision through astig-matism, but as the eye is underwater with the cornea havingno refractive power, a non-spherical cornea does not give adistorted retinal image.Elasmobranchs live in a wide range of marine habitatsfrom shallow coastal waters, open ocean, mesopelagic(200–1000 m), and bathypelagic environs (1000–4000 m)with very different photic characteristics. It should not sur-prise us then that the eyes of these fish are widely varying. Insize this may range from the pelagic sharks such as theappropriately named bigeye thresher shark Alopiassupercilliosis with a globe 62 mm in diameter down to the7 mm diameter eye of the coffin rayHypnos monopsterygnius(Lisney and Collin 2007). Some hold that the fish with thesmallest eyes tend to live in coastal areas where the water isoften turbid because of the concentration of plankton andorganic matter suspended in the water rendering vision diffi-cult and where sharks tend to rely on olfaction andelectrodetection more than vision. To give specific details astudy comparing two shark species with different ecologies,Litherland et al. (2009a,b) noted that the eyes of theshortspine spurdog Squalus mitsukurii, inhabiting deepwaters of the coastal shelf are adapted for vision in a dimlight environment with a large eye and a lens anteriorlyplaced in the eye and containing short-wavelength absorbingfilters optimising detection of bioluminescent prey(Fig. 4.1a). The sandbar shark Carcharhinus plumbeus onthe other hand inhabits shallow coastal waters and has acomparatively smaller eye with a lens placed more centrallyin the globe (Fig. 4.1b).We talk of eye size in these fish but must remember thatmany species of fish, and particularly larger sharks growcontinually through life and while this involves an increasein body size it also has relevance to globe dimensions.Increasing eye size increases the resolution of the retina asfish age. In addition, this increase in eye size changes the sizeof the horizontal visual streak (region of high acuity in theretina), as more retinal neurons are added to the periphery ofthe retina with increasing age (Litherland et al. 2009a,b).The extraocular muscles of many sharks contain a largenumber of oxidative fibres suggesting endothermy(Tubbesing and Block 2000) and in some species such asthe bigeye Thresher Alopias supercilliaris the large eye issupported thermally by an orbital rete mirabile which heatsthe eye (Weng and Block 2004). Indeed, many sharks have awarming mechanism to heat the eye and brain, associatedwith an orbital rete. In the laminiod sharks, this warming isproduced by hyoidean and pseudobranchial arteries (Blockand Carey 1985). This increase in temperature is thought toincrease visual acuity and temporal resolution, important infast-moving predatory fish (Collin 2018).48 D. WilliamsAll elasmobranchs have an unusual, unique structurecalled the optic pedicel, a prop-like structure spanning theorbit from the cranium to the posterior pole of the eye(Fig. 4.2, Collin 2018). Fossil evidence suggests that isstructure first appeared in Placoderm fish during the Devo-nian period around 400 million years ago. The placodermsbecame extinct but the pedicel has been retained in theelasmobranchs. The junction between this cartilaginous rodand the back of the eye often appears as a ball and socketsynovial articulation thus seeming to provide a supportingmechanism as the eye rotates in the large orbit. The opticpedicel is made up of hyaline cartilage with closely packedcollagen fibrils that provide simultaneous firm support andelastic properties. There appears to be a correlation betweenthe size of the eye and the area of articulation at the posteriorpole of the eye supporting the hypothesis that the pedicelprovides additional support to large-eyed sharks, althoughthere is also a suggestion that the pedicel, attaching close tothe optic nerve, aligns the eyes into a default position follow-ing compensatory eye movements when the fish dives. Thepedicel is particularly well developed in rays in which theeyes do protrude more from the skull than they do in sharks,further supporting the view that the pedicel itself providessupport.Eye movement in sharks is considered to be controlledthrough a neural mechanism known as efference copy, givingcompensatory globe movements occurring relative to bodymovements as the shark swims. This helps keep the visualimage stable during movement. Research on thesemechanisms has, however, only been undertaken on captiveFig. 4.1 Comparison of eye size relative to the body in (a) the Shortspine spurdog Squalus mitsukurii, and (b) the White sandbar sharkCarcharhinus plumbeusFig. 4.2 The eye of a shortfin devil rayMobula kuhlii demonstrating the optic pedicel (black arrows) and the optic nerve (white arrows). (Courtesyof Marie-Aude Genain)4 Ophthalmology of Cartilaginous Fish: Skates, Rays, and Sharks 49sharks and we know little about ocular movements in free-swimming sharks. The elasmobranchs have the sixextraocular muscles seen routinely in many other vertebrates,namely the four rectus muscles, the superior oblique and theretractor oculi muscles. In addition, some species such as thebamboo shark Chiloscyllium punctatum and wobbegongOrectolobus maculatus have two additional muscles thatinsert onto the rim of the optic pedicel, originating on thecranium (Collin 2018). These fish are benthic and haveobliquely constricting pupils with the novel musculatureacting in the same direction as the pupil axis, so these maybe important in directing globe rotation to optimise visualfunction. Another example lies with the inferior obliquemuscle of the giant guitarfish Rhynchobatus djiddensis,which is massively enlarged and originates on the ventralaspect of the neurocranium instead of the typical originationon the anteriomedial wall of the orbit (Tomita et al. 2016).Normally the muscle rotates the eye, but the inferior obliquemuscle of the giant guitarfish pulls the eye inward and ven-trally. This arrangement is also found in some other benthicbatoids such as the Rhinobatidae, Pristidae and Rajidae(Shirai 1992). Why these batoids have such profound globeretraction is unclear. It may be that this occurs during feedingor to protect the eye from trauma from coral (Fig. 4.3a).Fish do not generally have eyelids since underwater theirocular surface does not need the same level of protection thatis required in terrestrial vertebrates although parascyliidsharks have an unusually mobile upper eyelid; Tomita et al.2015). Considering, sharks do not exhibit blepharospam thatwould protect the eye in other vertebrates, and thus profoundglobe retraction may provide a similar protective mechanism.Having said that, many sharks are unusual (e.g. hemigaleid,carcharhinid and sphyrnid sharks) in that they have a well-developed third eyelid, comprised of a dense lamina of con-nective tissue covered in placoid scales (Fig. 4.3b–d) (Tomitaet al. 2015). The nictitating membrane in these fish is highlymobile—during feeding the closure of the nictitating mem-brane is coordinated with jaw opening, and it can completelycover the eye in some species (Fig. 4.3d). Protection of theeye is very important at the moment of prey capture and othercollision incidents, hence the rapid movement of this adnexalstructure. Traumatic lesions periocularly are commonly seenin wild sharks, both from conspecific aggression, otherpredators or even prey, and sadly from humans (e.g. boatmotors—see Fig. 4.4). Successful globe retraction can sparethe globe, leaving only impressive scars around the eye(Fig. 4.4b). This protrusion of the third eyelid is occasionedby a muscle the levator palbebrae nictitans first described byJohannes Muller (1843) and apparently innervated by cranialnerve III.An interesting region of translucent skin just dorsal to theeye has been described in Etmopteridae sharks (Claes et al.2014). This region contains photophores directed into the eyetowards photoreceptors, a strategy for increasing photon cap-ture while living in the dark mesopelagic zone with depen-dence on detection of bioluminescence.The cornea in most sharks is relatively thin (160 umcompared to 630 um in dogs and 540 um in humans) andhas a multi-layered epithelium (i.e. about 12 cell layers)comprising a greater proportion of the corneal thicknessthan in terrestrial vertebrates (Fig. 4.5a). The surface of theepithelium is modified with numerous microvilli andmicroplicae, presumably to increase the surface areaoptimising the exchange of nutrients and removal of wasteproducts. Deep to this stratified squamous epithelium is itsbasement membrane abutting onto the most superficialstroma, which unlike most subprimate mammals has an acel-lular superficial Bowman’s layer. The corneal stroma insharks contains lamellae that are extremely organised in aparallel fashion (Fig. 4.5b). At the internal face of the stroma,where one might expect Descemet’s membrane and the cor-neal endothelium in a mammal, there are often no equivalentstructures. It may be that the key role of the corneal endothe-lium in maintaining the correct hydration of the cornea is notneeded in these cartilaginous fish. One reason for this may bebecause a complex network of thick and thin sutural fibresspan the stroma inhibiting the stromal swelling which wouldnormally be expected without an endothelial layer to pumpwater out of the corneal stroma (Fig. 4.5c).Trauma is often seen in the corneas of both wild andcaptive elasmobranchs, and post-corneal rupture phthisisbulbi is not uncommon in wild sharks (Fig. 4.6). Indeed,the one paper in the literature on enucleation in these fishdetails the surgery following trauma during mating in acownose ray which the authors report is commonly seen atthis time in these species both in captivity and in the wild(Abraham Gabriel et al. 2018). Management of conspecificinteractions during mating season is imperative in captiveelasmobranchs to reduce trauma (Wildgoose and Lewbart2001).Another cause of trauma is infestation with ocularparasites (Fig. 4.7a). For example, the sea louseLeopeophtheirus actus, a copepod parasite, is a serious path-ogen in captive elasmobranchs as demonstrated by one pub-lication documenting the fatal results of infestation whichfirst manifest as abnormal behaviour, cessation of feedingand corneal opacification progressing to further ocular andsystemic deterioration requiring euthanasia (Kik et al. 2011).This is not only a problem in captive fish though, asdemonstrated by Benz and colleagues’ report on ocularlesions associated with attachment of copepods to the corneasof Pacific sleeper sharks in Prince William Sound, Alaska(Benz et al. 2002). A high proportion of these sharks wereaffected yet not with the fatal results of the cownose raymentioned previously. Parasitic species should not be50 D. Williamsconfused with atraumatic mutualism, such as the cleanerwrasse Labroides dimidiatus (Fig. 4.7b).Iris and PupilThe uveal tract of elasmobranchs is important in thatelasmobranchs possess highly movable pupils and in thisway differ from teleost fish in which the pupils are generallyimmobile or less mobile. This difference may relate to therapid movements of sharks up and down the water columnrequiring instantaneous changes in ocular sensitivity. Thislinks with the fact that deep-sea dwelling species have largeimmobile pupils while it is species living in shallow brightlylit waters which have rapid iridal movements and the abilityto constrict the pupil to a slit. The exception, so they say,proves the rule and it has to be said that the shortspinespurdog which moves from epipelagic areas to a depth of athousand metres and yet appears not to have any change inpupil shape or diameter (Litherland 2009)! As in all speciesFig. 4.3 Globe protection in sharks. (a) Great white sharkCarcharodon carcharias exhibiting profound globe retraction as itattacks prey. Note that only the conjunctiva is visible. (b) Third eyelidprotrusion noted in a blue shark Prionace glauca (b) as a protectivemechanism as it struggles between protective cage bars. Normal thirdeye protrusion in a Tiger shark Galeocerdo cuvier showing (c) partialocular coverage and (d) complete ocular coverage. (a—Used withpermission from Allessandro De Maddalena/Shutterstock.com. b—Used with permission from Richard Robinson/Nature Picture Library/Science Photo Library. c, d—Used with permission from Jeff Rotman/Alamy Stock Photo)4 Ophthalmology of Cartilaginous Fish: Skates, Rays, and Sharks 51http://shutterstock.comthe ciliary body produces the aqueous humour but we haveno understanding of the relative importance of the trabecularmeshwork or unconventional uveoscleral pathway in thedrainage of aqueous in elasmobranchs.Sharks generally have a pupil which closes to a slit inwell-illuminated environments. Pupil shape varies greatlyacross species, from diamond shape in the tiger sharkGaleocerdo cuvier (Fig. 4.8a) to variousforms of ovoid toslit shapes, such as the ever-common vertical ovoid slit seenin the blue shark Prionace glauca, lemon shark Negaprionbrevirostric and whitetip reef shark Triaenodon obesus(Fig. 4.8b), vertically ovoid as in the milk sharkRhizoprionodon acutus (Fig. 4.8c), or horizontally ovoid asin the basking shark Cetorhinus maximus. Pupils can also bequite open and round, as in the scalloped hammerhead sharkSphyrna lewini (Fig. 4.8d), or can be very narrow andinflected diagonally as in the nurse shark Ginglymostomacirratum, cat shark Scyliorhinidae sp., the tassled wobbegongshark Eucrossorhinus dasypogon, and in the Angel sharkSquatina squatina (Fig. 4.8e,f). Some slit pupils, such asthat of catsharks Scyliorhinidae sp. and the small-spotteddogfish Scyliorhinus canicular have a pupil which, whenconstricted, forms a slit with a double pupil, having a smallaperture at each end of the slit (Fig. 4.8e). Based on studies ofoptics in other species, this may enable maintenance of ashallow depth-of-field while reducing the overall light tothe retina, similar to the effect produced by a Hartmannmask (a previous study compared the gecko iris to a Scheinerdisk which actually only has two holes, whereas a Hartmannmask can have multiple holes) (Murphy and Howland 1986).The iris of some shark species, notably lemon sharksNegaprion brevirostris, has been noted to have focal areasof absent iridal tissue (Fig. 4.9) (Personal communicationBret A. Moore). In these areas, light is able to pass freelyinto the posterior segment of the eye. In some cases, the holesare confluent with the pupil forming a notch (Fig. 4.9c). Thepurpose or cause of such a structure or malformation isunknown.Even more remarkable perhaps are the irides and pupils ina number of rays and skates (Fig. 4.10). The dorsal margin ofthe pupil is expanded and crenulated into an operculum witha number of different forms, from variable numbers of finger-like projections as in the yellow stingray Urobatisjamaicensis (Fig. 4.10a–c) and the thornback ray Raja cla-vate (Fig. 4.10d), to a plate-like projection as in the Kuhl’smaskray Neotrygon kuhlii (Fig. 4.10e) or the blue-spottedribbontail ray Taeniura lymma (Fig. 4.10f). As demonstratedin Fig. 4.10e, the operculum can nearly occlude the pupil andthus can provide excellent blocking of light, but whencontracted results in a wide-open pupil with only mild dorsalshading (Fig. 4.10f).The LensAs with other fish, the cornea plays little or no part inrefraction since light is passing not from air through theFig. 4.4 (a) A normal left eye of a whale shark Rhincodon typus. (b)The same whale shark whose right periocular tissue is showing exten-sive scars following past trauma from a boat motor. This is anunfortunately common side effect of diving tours to swim with thesebeautiful animals. (Photographs and discussion courtesy of David G.Heidemann and Bret A. Moore)52 D. Williamscornea, but rather from water to the cornea where refractiveindices are very similar. This means that the lens is the onlyrefractive element in the shark eye and thus is, in all fishspecies, largely spherical. The high concentration of crystal-line proteins in the lens gives it a high refractive index,optimising its image-forming power. Both sharks and rayshave multifocal lenses, as the concentration of this refractileprotein is graded across the lens reducing spherical aberration(Gustafsson et al. 2012). Chromatic aberration is alsominimised but it is also important to realise that spectralfilters in the cornea and the lens are key in reducing thetransmission of damaging ultraviolet light encountered inshallow coastal waters. The absorption of these shortwavelengths also reduces light scatter, which is greater atshorter wavelengths. However, there are exceptions withinsuch a diverse taxonomic group. In the lemon sharkNegaprion brevirostris for instance, the lens is ellipticalwith the equatorial diameter being around 13% longer thanthe axial diameter (Hueter and Gruber 1982). The bluenosedstingray Dasyatis sayi has an even more markedly ellipticallens with the difference in diameters being around 18%,while in the sandbar shark Carcharhinus plumbeus it isaround 16% and in the nurse shark Ginlymostoma cirratumit is 15% (Sivak 1989). The reason for this unusual differencemay relate to the packing of secondary lens fibres with thetapering anterio-posterior terminal ends leading to anincreased equatorial diameter compared to the axial diameter.The shark keeps growing throughout life as does its lens butthe ratio of globe to lens size changes (thus, the lens growsmore slowly). Similar to dating trees by the number or ringsthey have, the lens crystalline proteins in the centre of the lensare as old as the animal itself and thus provide a perfect targetfor radiocarbon dating of lens proteins. Studies on lensesfrom Greenland sharks Somniosus microcephalus haveshown them to be at least 272 years old (Quaeck-Davieset al. 2018), and perhaps even over 400 years old (Nielsenet al. 2016). Despite these impressive ages and ever-growinglenses, cataracts are extremely rare (Fig. 4.11). In fact,Greenland shark lenses are typically crystal clear withouteven nuclear sclerosis! Perhaps with the sharks lies the keyto unlocking the treatment for cataract prevention in humans.The biochemistry of shark lenses differs from that of othervertebrates (Zigman 1990). Shark gamma crystallins have amuch lower methionine content than that of teleost fish, muchmore similar to that of mammals. These proteins have asignificantly different tertiary structure from those of teleostfish. We know that the elasmobranchs separated from theplacoderms many millions of years before the teleosts sepa-rately evolved but whether this similarity of gammacrystallins between sharks and mammals is convergence orreflective of true evolutionary similarity is unclear. The mainlens protein is alpha-crystallin and this protein appears tohave changed little between the dogfish which appearedFig. 4.5 Microanatomy of the cornea of elasmobranchs. (a) The corneaof the leopard shark Triakis semifasciata showing the tremendous thick-ness of the epithelium compared with the stroma. (b) The cornea of astingray species showing remarkably parallel stromal collagen lamellae.(c) Sutural fibre spanning collagen lamellae in the Caribbean reef sharkCarcharhinus perezii cornea. (Courtesy of the Comparative OcularPathology Laboratory of Wisconsin)4 Ophthalmology of Cartilaginous Fish: Skates, Rays, and Sharks 53420 million years ago and the cow which evolved 160 millionyears ago (de Jong et al. 1988). The chaperone activity ofdogfish alpha-crystallin was found to be similar to that ofbovine alpha-crystallin in preventing thermal damage ofother crystallins but the dogfish protein was three timesmore effective at preventing insulin precipitation (Ghahghaeiet al. 2009). Perhaps given that dogfish live to more than30 years and that cattle generally live for half of that duration,having a greater chaperone activity to protect lens proteinsfrom photo-oxidative damage would seem eminentlyreasonable.Although we have not yet established the prevalence ofcataracts in either captive or free-living elasmobranchs, anec-dotal evidence suggests a lower level of lens opacities inthese fish. This would certainly make sense, consideringthat the previously noted Greenland shark lives for morethan 400 years all the while maintaining perfect lenticularclarity (compared to other long-living species, such asFig. 4.6 (a) The eye of a normal lemon shark Negaprion brevirostris. (b) A lemon shark with marked phthisis bulbi likely from trauma.(Photographs and discussion courtesy of David G. Heidemann and Bret A. Moore)Fig. 4.7 (a) A copepod parasite, Ommatokoita elongata, attached tothe cornea of a Greenland shark Somniosus microcephalus. This parasitespecies is specific to Greenland sharksand Pacific sleeper sharks andcan cause severe visual impairment. However, in these species, visualcompromise does not seem to be of significant detriment on survivalseeing that the Greenland shark can live to be over 400 years old basedon radiocarbon analysis of the ocular lens (Nielsen et al. 2016). (b) Acleaner wrasse Labroides dimidiatus removing dead skin andectoparasites from the ocular surface of a blue-spotted ribbontail rayTaeniura lymma, a non-pathologic exhibition of mutualism. (a—Usedwith permission from Paulo Oliveira/Alamy Stock Photo. b—Use withpermission from Louise Murray/Science Photo Library)54 D. WilliamsFig. 4.8 Pupil shapes of sharks. (a) The diamond-shaped pupil of aTiger shark Galeocerdo cuvier, (b) vertical ovoid-slit pupil of theWhite-tip reef shark Triaenodon obesus, (c) vertical ovoid pupil in ayoung milk shark Rhizoprionodon acutus, (d) open and round pupil in ascalloped hammerhead shark Sphyrna lewini, (e) obliquely oriented slitpupil exhibiting Scheiner’s disk phenomenon in a cat sharkScyliorhinidae sp., and (f) an obliquely oriented slit pupil in an Angelshark Squatina squatina. (a—Used with permission from HannesKlostermann/Alamy Stock Photo. b—Used with permission by JeffRotman/Alamy Stock Photo. c—Used with permission by SuzanneLong/Alamy Stock Photo. d—Used with permission by Jeff Rotman/Alamy Stock Photo. e—Used with permission by Kurit Afshen/Shutterstock.com. f—Used with permission from imageBROKER/Alamy Stock Photo)Fig. 4.9 Normal eyes of lemon sharks Negaprion brevirostris showingunique focal areas of absent iridal tissue that are not uncommon in thisspecies. The cause or function is unknown. (a) Note several holes in theiris dorsally (less common) and ventrally. (b) A side view shows slightconcavity ventrally at the 6 o’clock position where iris tissue is absent.(c) a large area of absent iridal issue ventrally and confluent with theventral aspect of the pupil creating a notch defect. (Photographs anddiscussion courtesy of David G. Heidemann and Bret A. Moore)4 Ophthalmology of Cartilaginous Fish: Skates, Rays, and Sharks 55http://shutterstock.comFig. 4.10 Normal iris structure in various rays. (a, b) A yellow stingrayUrobatis jamaicensis with a veil-like operculum with 3 finger-likeprojections limiting light entering the pupil. (c) Another yellow stingrayusing sand to camouflage the eye. (d) A thornback ray Raja clavata withan operculum with more finger-like projections and greater pupilblocking. (e) A Kuhl’s maskray Neotrygon kuhlii whose pupil is nearlycompletely occluded but a round operculum that fits the shape of thepupil. (f) Upon contraction of the operculum, the pupil is exposed toenable entry of more like as demonstrated by this blue-spotted ribbontailray Taeniura lymma. (a–c—Images courtesy of David G. Heidemann.d—Used with permission from Rui Palma/Shutterstock.com. e—Usedwith permission from Ethan Daniels/Shutterstock.com. f—Used withpermission from Andre Seale/VWPICS/Science Photo Library)56 D. Williamshttp://shutterstock.comhttp://shutterstock.comhumans and elephants, where cataracts to some degree arealmost an inevitability). Other than greater lens chaperoneactivity as found in the dogfish, it must be noted also that alow level of cataractogenesis may be linked with changes incorneal coloration and ultraviolet filters quite as much asother biochemical adaptations within the lens itself. Or per-haps super-cooling our eyes and bodies while livingimmersed in the frigid artic depths as does the Greenlandshark, is the key to a long life free of cataracts!Accommodation in sharks occurs through the anterogrademovement of the lens mediated by the protractor lentis mus-cle in the pseudocampanule located in the ventral papilla ofthe ciliary body. The lens is also supported by the suspensoryzonule. It is difficult to determine the accommodative rangeof sharks; however, Hueter determined free-swimming lemonsharks (Negaprion brevirostris) to be emmetropic, but whenrestrained they became hyperopic, probably due to the inhi-bition of accommodation during restraint (Hueter et al. 2001).RetinaThe retina of most elasmobranchs is duplex with rods andcones allowing vision in scotopic and photopic conditions,although some species, and understandably the deep seaspecies, can have rod-dominated retinae (Bozzano et al.2001; Hart et al. 2011; Claes et al. 2014). Even in speciesliving in relatively photopic environments the proportion ofrods and cones can be highly variable between differentspecies (Partridge et al. 1989). For example, the ratio is 4:1in the white shark (Carchorodon carcharias) while it is morethan 100:1 in the birdbeak dogfish (Mustelus canis). Theelasmobranch retina is quite different from that of theteleosts: retinotopic movements are critical in the teleosts toalter retinal sensitivity but they are not seen to a similardegree in the majority of fish such as sharks and rays.Rod photoreceptors have one photopigment (RH1), butbetween species the absorption maximum of the pigment canbe substantially varied. Deep-sea bioluminescent sharks havebeen shown to have rhodopsin maximum absorbance valuesbetween 485–487.5 nm (Claes et al. 2014). In other sharksthese visual pigments are varied—just as one example therods of the juvenile lemon shark (Neogoprion brevirostris)contain a porphyriopsin with a maximal absorption at 522 nmwhile the adult of the same species uses a rhodopsin absorb-ing maximally at 501 nm (Cohen et al. 1990). This differenceperfectly matches the change in behaviour as the fishmatures: the juvenile sharks inhabit the shallow inshorewaters which have copious organic matter diffusing thelight to longer wavelengths while the adults live in deeperFig. 4.11 Cataract in a free-living pygmy shark Euprotomicrus bispinatus. (Used with permission from Doug Perrine/Nature Picture Library/Science Photo Library)4 Ophthalmology of Cartilaginous Fish: Skates, Rays, and Sharks 57offshore water with a spectral shift to shorter bluewavelengths.Across the animal kingdom, the cone visual pigments aretermed SWS1, SWS2, RH2, or LWS (these acronymsdenoting “short-wavelength-sensitive”, “rhodopsin-like”,and “long-wavelength-sensitive”, respectively. In thechondrichthyan fishes, the SWS1 and SWS2 opsin genesappear to have been lost following its separation from thebony fishes (Osteichthyes) around 460 million years ago, thisbeing prior to the divergence of the holocephalan chimerasand the elasmobranch sharks, skates, and rays around420 million years ago. Batoids, sawfish and skates have adichromatic vision while sharks have the RH1 rod opsin andonly one cone photopigment, so are cone monochromats.Gene sequencing, however, shows that this reversion fromcone dichromacy to monochromacy has happened at leastthree times at different points in evolution. The details are toocomplex to be included in this short review chapter andreaders are directed towards Hart and colleagues’ recentpaper on the subject (Hart et al. 2020).In addition to considering photoreceptor absorptionspectrums, we should also note the topographicalorganisation and visual acuity of the retina of elasmobranchs(Lisney and Collin 2007, 2008). Sharks inhabiting structur-ally complex environments have a localised area of highphotoreceptor and ganglion cell density while those livingin less complex two-dimensional environments such as theopen ocean have a profound visual streak. Additionally,depth of inhabitancy may also play a role, as pelagic speciestend to have an area centralis (or more than one),benthopelagic sharks display wide horizontal streaks, andbenthic sharks tend to have narrow horizontal streaks (Claeset al. 2014). Collin’s group has undertaken a substantialamount of research on the topographical arrangement of theretina across the elasmobranchs and have described thesearrangements beside their behavioural and ecologicalcorrelates.One particular example can be demonstrated inthe deep-sea sharks: a lanternshark Etmopterus lucifer has2 area centrales within a horizontal streak that likely enablesdetection of bioluminescent markings on the flanks ofconspecifics, while the viper dogfish Trigonognathus kabeyaihas a dorsally extended area centralis that enables adjustmentof the strike by its peculiar jaws in the ventrofrontal visualfield (Claes et al. 2014). Shaun Collin’s review ‘Scenethrough the eyes of an apex predator: a comparative analysisof the shark visual system’ (Collin 2018) is an excellent placeto begin understanding the correlation between ocular anat-omy and physiology, retinal topography, visual fields, andbehaviour. As would be expected, there is a close correlationbetween the visual fields and the placement of retinalspecialisations within the visual space.For a group of animals inhabiting a wide range ofenvironments and that in some ways has changed very littleover hundreds of millions of years, the cartilaginous fish havesuperbly evolved eyes to optimise vision in these differentarenas. Despite vision not being their primary sensory input,the eyes of many species are critical for survival. 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Fish Bull 102:221–229Wildgoose WH, Lewbart GA (2001) Terapeutics. In: Wildgoose WH(ed) BSAVA manual of ornamental fish. BSAVA, pp 237–258Zigman S (1990)Comparative biochemistry and biophysics of elasmo-branch lenses. J Exp Zool 256(S5):29–404 Ophthalmology of Cartilaginous Fish: Skates, Rays, and Sharks 59https://doi.org/10.1126/science.aaf1703https://doi.org/10.1126/science.aaf1703Ophthalmology of Osteichthyes: Bony Fish 5Christine A. Parker-Graham, Brittany N. Stevens, June H. M. Ang, EstebanSoto, David L. Williams, Jennifer Kwok, and Bret A. Moore# Chrisoula SkouritakisC. A. Parker-Graham (*)US Fish and Wildlife Service, Lacey, WA, USAe-mail: christine_parker-graham@fws.govB. N. StevensAquarium of the Pacific, Long Beach, CA, USAe-mail: brittanystevensdvm@gmail.comJ. H. M. AngUnited Veterinary Clinic Blk 107, Singapore, Singaporee-mail: hmjuneang@gmail.comE. SotoDepartment of Medicine and Epidemiology, School of VeterinaryMedicine, University of California, Davis, CA, USAe-mail: sotomartinez@ucdavis.eduD. L. WilliamsThe Queen’s Veterinary School Hospital, University of Cambridge,Cambridge, UKe-mail: dlw33@cam.ac.ukJ. KwokVeterinary Emergency & Referral Group, Brooklyn, NY, USAe-mail: info@verg-brooklyn.comB. A. MooreDepartment of Small Animal Clinical Sciences, College of VeterinaryMedicine, University of Florida, Gainesville, FL, USAe-mail: bretthevet@dvm.com# Springer Nature Switzerland AG 2022F. Montiani-Ferreira et al. (eds.), Wild and Exotic Animal Ophthalmology, https://doi.org/10.1007/978-3-030-71302-7_561http://crossmark.crossref.org/dialog/?doi=10.1007/978-3-030-71302-7_5&domain=pdfmailto:christine_parker-graham@fws.govmailto:brittanystevensdvm@gmail.commailto:hmjuneang@gmail.commailto:sotomartinez@ucdavis.edumailto:dlw33@cam.ac.ukmailto:info@verg-brooklyn.commailto:bretthevet@dvm.comhttps://doi.org/10.1007/978-3-030-71302-7_5#DOIIntroductionThree extant classes of vertebrates are considered under thelarger umbrella of fish: Agnatha (Chap. 3), Chondrichthyes(Chap. 4), and Osteichthyes. As previously discussed inChap. 3, the two surviving groups of Agnathans, lampreysand hagfish, are rarely encountered in veterinary medicine.Also discussed, Chondrichthyes are notable for havingskeletons comprised of cartilage rather than bone. One ofthe two extant subclasses of Chondrichthyes,Elasmobranchii, is common throughout veterinary literatureand aquatic medicine practice and includes sharks, rays, andskates (the subclass Holocephalii includes chimeras, whichare not commonly encountered in clinical practice). How-ever, most exotic animal practitioners will encounter fish inthe third and largest class: Osteichthyes, which includesteleosts. Over 27,000 species within nearly 450 families ofteleost or ‘truly bony’ fish have been described.Within the Osteichthyes, the diversity is tremendous,ranging from the ocean-dwelling giant oarfish (Regalecusglesne), which measures nearly 8 m long, and the oceansunfish (Mola mola) weighing up to 1000 kg, to the minutemale anglerfish (Photocorynus spiniceps) measuring just6.2 mm and who spends his life fused parasitically to hisfemale mate. Perhaps the widely disparate habitats are thereason for such diversity, whereby fish may live in colorfulreefs, brackish estuaries, the monotonous open ocean, or thebioluminescent ocean depths. Given the dramatic variationacross species, as well as the fantastic differences betweendifferent aquatic habitats, the visual systems of fish are asdiverse as one could expect. Indeed, an entire book could bewritten on just the visual system of fish, and readers aredirected to Nichol’s text “The Eyes of Fishes” (Nichol1989) for substantially more information than what can beprovided here.We will explore the visual system of fish, but our focuswill be on a clinical approach to fish ophthalmology. Fish arepopular pets in North America and numerous species areimportant for protein production worldwide. Ornamentalfish are the most commonly kept pets in the USA accordingto a recent survey by the American Veterinary Medical Asso-ciation (AVMA 2017). The demand for veterinarians familiarwith fish disease and treatment is rapidly expanding as clientdemands and government regulations regarding drug use infish change. Ocular diseases and disorders are a commonpresenting complaint for fish patients and systemic diseaseoften manifests ocular pathology, making it important for theexotics practitioner to be familiar with basic fish ophthalmol-ogy. Despite the current paucity of information on the diag-nosis and treatment of ophthalmic diseases in fish, we hopethat this framework will enable future growth in research andclinical finesse in fish ophthalmology.Visual Ecology and the Aquatic EnvironmentLight is absorbed by water in varying amounts depending onits wavelength, with pure water being almost transparent at460 nm but absorbs relatively strongly at wavelengths aboveand below this value. This apparently simple fact is compli-cated for aquatic organisms considering that the water theylive in is not pure; dissolved pigments and suspendedparticles absorb and scatter light differently in differentenvironments. Where phytoplankton grow in coastal waters,chlorophyll strongly absorbs below 435 nm as do dissolvedyellow pigments known as gelbstoff (Jerlow 1978). Oceanwaters are mostly transparent at around 475 nm while overthe continental shelf maximum transmission is shifted tohigher wavelengths around 500–530 nm. Turbid coastalwaters are only transparent at higher wavelengths up to580 nm where absorption increases. In shallow coastal watersirradiance is broad spectrum, while in clear deep oceanicwaters the downwelling light is blue although its intensitydrops considerably the deeper one goes. In deep ocean waterslight from bioluminescent organisms provides more illumi-nation than does downwelling light and this can be of varyingwavelengths. We have to consider more than merely wave-length though. Sunlight is polarized through atmosphericscattering and water absorbs polarized light differentiallydepending on the direction of incident sunlight. All thesefactors will have considerable influence on the anatomy andphysiology of the eyes of aquatic organisms such as fish.Fish vision has been a topic of intense research interestand thanks to laboratory species, such as the well-studiedzebrafish (Danio rerio), the retina has been well described.While fish do possess additional sensory systems, like alateral line, we know that vision is important for many spe-cies living in aquatic zones that have clear media, receivesunlight, or bioluminescence. Prominence of the eyes can beseen early in development (Fig. 5.1), and eyespots can evenbe detected with close examination of the caviar that you mayhave recently enjoyed (Fig. 5.1d)! Blind fish are often smallerthan their conspecifics and have a lower feed conversion rate(Williams 2012). Like the globe, the avascular teleost retinacontinues to grow throughout the animal’s life. A germinalzone at the margin of the retina creates additionalphotoreceptors as the retina stretches. While the clinicalimplication of the germinal zone is unclear, it may be possi-ble for fish to regenerate damaged retinal tissue. In somespecies the optic nerve branches into several optic discs inthe retina. Many species possess a tapetum lucidumcomprised of guanine and triglycerides mixed with melaningranules residing in the cytoplasm of the retinal pigmentepithelium (RPE). Some fish retinae contain rods and fourdifferent types of cone photoreceptors (compared to three inhumans). With this fourth cone it is thought that fish can62 C. A. Parker-Graham et al.differentiate light from different spectra as well as light ofdifferent polarizations, similar to birds and insects (Stoskopf1993; Jurk 2002). The perception of differences indownwelling polarized light may trigger important behav-ioral and migration cues. Other fish, such as those of thedeep sea, may be rod monochromats.Without a PLR to protect the retina againstthe phototoxiceffects of high light conditions, fish have developed a uniqueprotective mechanism: the retinomotor response. There aremicroscopic folds within the RPE, in bright light where colorvision is more important and less light sensitivity is neededrods move into these recesses and cones emerge. In low lightconditions the opposite occurs, with rods moving out of theRPE to absorb as much light as possible. Cytoplasmic pig-ment in the cells comprising the RPE can also migrate inresponse to light; in low light conditions, pigments migrateposteriorly within the cell to expose the surface of the photo-receptor and in the bright light the pigment migratesanteriorly to screen the photoreceptors. Both protective pro-cesses take approximately one to two hours to respond tolight changes; this time lag is important to keep in mind whenmoving fish from dark transport tanks to brightly-lit examspaces as immediate and prolonged exposure to bright lightscan result in phototoxic injury to the retina (Williams 2012).Additional aspects of fish visual ecology will be introducedas ocular anatomy is discussed.Structure and Function of the Fish EyeThere is wide species variation in ocular anatomy amongteleosts, ranging from the degenerate to absent eye of theblind cave fish, or the Mexican tetra Astyanax mexicanus, tothe complex eye of the four-eyed fish (Anableps spp.) thatallows this species visual acuity in air and water. The basicstructure of the Osteichthyes eye is similar to that of terres-trial tetrapods, but includes several adaptations for theiraquatic life histories. In most species, the eyes are positionedlaterally on the head, residing within a complete bony orbit(Fig. 5.2a), although many exceptions occur both in orna-mental fish with large protruding eyes and often rotated eyes(Fig. 5.2b) and those in the wild such as flouder (Fig. 5.2c).Fig. 5.1 Bullseye jawfish Opistognathus scops exhibiting oral eggincubation. Note the fluorescent corneal coloration (a) due to the pres-ence of chromatophores. The transparent eggs reveal already well-developed eyes in the embryos (b, c—arrow). (d) Note the visibleeyespots of sturgeon caviar, representing pigmented uveal tissue at anearlier stage of development. (a–c—Courtesy of David G. Heidemann,d—Courtesy of Bret A. Moore)5 Ophthalmology of Osteichthyes: Bony Fish 63The eyes are generally antero-posteriorly compressed and aresupported by scleral ossicles and scleral cartilage (Jurk2002). Most fish cannot move the globe voluntarily andmust reposition their body to gyroscopically reposition theglobe. Unlike many terrestrial species the teleost eyecontinues to grow throughout the animal’s life.As in all birds and most reptiles, teleost fish have skeletalelements providing structural support to their eyes. Theseskeletal elements are however positioned differently andhave different developmental origins in teleost fish. Thescleral ossicles in fish form two half circles that encircle theeye around the equator and are known as the anterior andposterior ossicles. Ossicles are found within the scleral carti-lage and in the adult, a dorsal and ventral cartilaginouselement develops in the space between the anterior andposterior ossicles to completely encircle the eyeball (Franz-Odendaal and Hall 2006).Teleost fish have six extraocular muscles for ocular move-ment—the dorsal oblique, ventral oblique, medial rectus,dorsal rectus, ventral rectus, and the lateral rectus. Ocularmovement in the larval zebrafish starts with the optokineticresponse developing at 73 h post-fertilization (hpf) andmaturing to adult speed at 96 hpf. Similarly, reset movementsand the vestibulo-ocular reflex both begin developing ataround the same age, while spontaneous saccadic movementsappear last at around 81–96 hpf. Ocular movements developwithout the need for significant tuning through experienceand the environment (Easter and Nicola 1996, 1997). Therange of ocular motion varies among teleost species, from thelimited movement in the carp and goldfish Carassius spp. tothe extreme ventral rotational “blink” that mudskippers per-form for ocular rehydration (Al-Behbehani and Ebrahim2011). Some species such as Monacanthus spp. and thesand lance are capable of independent movement of theeyes, but most species show synchronized eye movement.Three types of spontaneous eye movements have beendescribed in teleost fish: saccades, which are short twitchescausing shifts in the angle of gaze; stretches, which arecaudo-ventral eye jerks; and slow movements, which areslow eye drifts (Easter 1971; Hermann and Constantine1971).As we noted above, the Osteichthyes fish comprise a largemultispecies group of chordates that inhabit almost allaquatic habitats on the planet. To support their variouslifestyles and niches, their ocular anatomies have evolvedmany unique adaptations. Perhaps the greatest challenge thepiscine cornea encounters in every species is the osmotic oneoccasioned by the aquatic environment in which fish live,thus we will first discuss this.Overcoming Osmotic Challenges to the EyeWhile all terrestrial species have evolved various ways tokeep the ocular surface lubricated and protected from debris,the main challenge that teleost eyes face from the environ-ment is osmotic. A mucus-covered epithelium, also known asthe dermal cornea, overlies the globes of teleost fish and iscontinuous with the skin and conjunctiva. It acts as a primaryphysical barrier against changes in corneal hydration to main-tain corneal transparency. Underneath the dermal cornea isthe scleral cornea, which is continuous with the globe itself.The epithelium of the cornea is relatively thin in thesaltwater teleost eye and is thicker in freshwater teleost fish(Edelhauser 2006). In the brown trout Salmo trutta, a fresh-water teleost, the corneal epithelium is comprised of twolayers: an outer cell layer that is easily sloughed off and amiddle epithelium of cuboidal cells with large numbers ofmitochondria and desmosomes. This epithelium has a basallayer of columnar cells overlying a thin basement membrane.The outer layer of the epithelium is freely permeable to water,but the inner layers act as barriers against trans-corneal waterFig. 5.2 (a) Payara Hydrolycus scomberoides skull showing a com-plete boney orbit common with most of the Osteichthyes. (b) Theprotruding and dorsally rotated eyes of a normal Choutengan celestialgoldfish Carassius auratus. (c) The eye of a normal flounder species(Bothus spp.—photographed in the Indian Ocean off the coast ofIndonesia) displaying eyes positioned outside the boney skull, almoststalk-like. (a—Used with permission by Erik Klietsch, Shutterstock.com. b, c—Courtesy of David G. Heidemann)64 C. A. Parker-Graham et al.http://shutterstock.comhttp://shutterstock.comand sodium movement (Edelhauser and Siegesmund 1968).Regarding the corneal epithelium, osmotic stress on the cor-nea has a significant relationship with cell densities, withepithelial cell densities being lowest in freshwater teleostcorneas, higher in estuarine species, and highest in saltwaterspecies (Collin and Collin 2006).The thinner corneal epithelium of the saltwater teleost isimpermeable to sodium and allows no net water movementbetween the environment and the eye. The thicker saltwaterteleost corneal stroma is comprised of an outer and an innerstroma loosely attached together. The outer stroma is morepenetrable to water than the inner layer. A thick Descemet’smembrane provides additional protection againstoverhydration of the outer stroma in this thick cornea byonly allowing salts and water to penetrate, while preventingcolloids such as hyaluronic acid from the anterior chamberfrom entering the cornea (Edelhauser 2006). Based on a studyby Smelser (1962), the teleost cornea does not appear to relyon aerobic metabolism to maintain correct corneal hydrationthe same way mammalian corneasdo. In freshwater teleostspecies, it is the corneal epithelium that plays the largest rolein protecting the cornea against the osmotic effects of theenvironment. Damage to the corneal epithelium in the rain-bow trout Oncorhynchus mykiss has shown to result in severecorneal edema and cataract formation (Ubels and Edelhauser1982).Further within the eye, intraocular water balance ismaintained with mucopolysaccharides that hold waterthrough the Donnan effect. These negatively chargedpolymers of chondroitin are present in varying quantities indifferent species in the aqueous humor and cornea. Sincemucopolysaccharides act to retain water, these polymers arefound in lower amounts in the corneas of freshwater fish thanthat of saltwater fish (Smelser 1962). Many species have theadditional requirement of being able to adjust intraocularosmolarity in response to environment changes. The rainbowsmelt Osmerus mordax is an anadromous (i.e., migratory)teleost from North America that overwinters underneath fro-zen coastal waters and relies on its vision for hunting preyduring the winter. In the winter, this species becomes almostisosmotic with seawater through osmotic water losses, whiletype II anti-freeze protein, glycerol, urea, and trimethylamineoxide accumulate in plasma and organs (Raymond, 1993).This increase in glycerol and osmolarity is also seen in thevitreous fluid as the eye enters a hyperosmotic state in orderto lower its freezing point. This species was found to expressthe proteins tubedown (Tbdn) and zonula occludens protein1 (ZO-1). Tbdn is associated with transmembrane permeabil-ity of vascular endothelium, while ZO-1 regulatesparamembrane permeability in the endothelium of the eye(Gendron et al. 2011). Tbdn and ZO-1 are also found inmammalian species (Gendron et al. 2000; Stevenson et al.1986), suggesting the application of these paramembrane andtransmembrane proteins in a wide range of species to alter theintraocular environment.The Ocular AdnexaWhile teleosts lack palpebrae, elasmobranchs possess eyelidsto varying degrees; some species have moveable eyelidswhile others have immobile eyelids that have fused over thecornea and become transparent to form a spectacle over thecornea (Fig. 5.3a). Although not the usual case, the cornea ofseveral teleost species may be covered by a layer of totallytransparent skin. A “corneal crevice” or “precorneal cham-ber” which is situated in front of the cornea or between itsmany layers may also be present. The function of this space isFig. 5.3 The ocular adnexa of Osteichthyes. (a) Subgross histologicimage of a normal Rockfish Sebastes spp. eye sectioned in a parasagittalplane. Note the extension of the conjunctiva into a precorneal mem-brane, or spectacle (arrows), overlying the cornea (asterisk). Pigmentedconjunctival epithelium may about the cornea at the limbus as in thecoral grouper (b), or it may extend into the cornea as shown in theFrench angelfish (c). (Grouper a—Courtesy of the Comparative OcularPathology Laboratory of Wisconsin. b—Courtesy of David G.Heidemann. c—Used with permission from VisionDive, Shutterstock.com)5 Ophthalmology of Osteichthyes: Bony Fish 65http://shutterstock.comhttp://shutterstock.comthought to enhance the mobility of the eye (Harder andSokoloff, 1976). Additionally, pigmentation from the con-junctiva often matches that of the periocular skin and canabut the cornea at the limbus (Fig. 5.3b) or even extend intothe cornea (Fig. 5.3c).The CorneaThe same basic cellular layers seen in terrestrial animalscomprise the fish cornea: epithelium, Bowman’s membrane,stroma, Descemet’s membrane, and endothelium (Collin andCollin 2001). Because of its importance in limiting watermovement across the cornea and reducing osmotic imbalancein the fish as a whole, the corneal epithelium in fish issignificantly more cellularly dense than terrestrial speciesand often rather thick (Fig. 5.4). Similar to terrestrial species,however, the epithelium of different species often has differ-ent morphologies. As a protective layer for the cornea, theepithelium is not obvious to the naked eye, however, somespecies such as the milkfish Chanos chanos have fleshyadipose eyelids (which do not contain adipose cells or lipids)that overlie the cornea and encase the eye in a translucentspectacle (Chang et al. 2009). These structures, usually foundin pelagic fish, also streamline the fish by making the eyecontinuous with the silhouette of the head. The cornealepithelia of teleost fishes contain different surfacemicrostructures that serve various functions. Microvilli areextensions of corneal epithelial cells that protrude perpendic-ularly from the cornea and are mostly seen in species thatperiodically spend time on land, such as the Australian lung-fish Neoceratodus forsteri and the salamanderfishLepidogalaxias salamandroides. Microplicae are small, elon-gated projections that form complex patterns over the cornealepithelium and are more common in freshwater teleost spe-cies. Microridges are the most common type of microprojec-tion on teleost corneas and are found even in the four-eyedfish Anableps anableps which has half of its cornea protrud-ing above the water (Simmich et al. 2012). Microridges arealso frequently found in teleost species inhabitingenvironments of high osmolality such as marine and estuaryhabitats, with the exception of the salamanderfish, whichlives in freshwater ponds that can develop high tannin levelsduring the dry season. Microridges are similar to microplicaebut are much longer in length and form fingerprint-likepatterns. Microholes have been found on the Australian lung-fish and the salamanderfish cornea. In the salamanderfish,these holes act as pores to allow mucus to be excreted frommucus-secreting granules and goblet cells (Collin and Collin2006). It is known that microvilli on the corneas of terrestrialanimals help maintain the tear film. In teleost fish, micropro-jections are considered to help increase surface area foroxygen diffusion into the cornea from the environment(El Bakary 2014) and microridges aid in the retention ofmucoid material protecting the surface of the eye (Hardinget al. 1974).Not all teleost fish possess a Bowman’s membrane, but inthose that do, this layer is present as a modified anterior zoneof the cornea underneath a stratified cuboidal epithelium andanterior to the corneal stroma (Mansoori et al. 2014). Thismembrane is unique in teleost fish in that collagen fibrils arearranged in an organized horizontal pattern, as opposed to therandom fibril arrangement found in mammals. This has beensuggested as a feature of adaptation to aquatic life(Edelhauser and Siegesmund, 1968).There are variations in corneal structure that depend oneach species’ lifestyle. Freshwater teleost corneas generallyhave thick epithelia, while the saltwater teleost cornealstroma is thicker and is separated into the outer and innerstromata. In deep-sea species, the corneal stroma may evenbe separated into three layers—the anterior scleral stroma,iridescent layer, and posterior scleral stroma (Collin andCollin 1998a). The two stromata may be loosely attachedvia a mucoid layer containing proteoglycans or by a granulartissue layer. The corneas of most teleost species are thin in thecenter and thicker in the periphery (Smelser 1962) and colla-gen fibril stromata are arranged in sheets with a slight rotationin fibrils in each layer (Winkler et al. 2015). Exceptions to thegeneral pattern in corneal thickness are found in the sandburrower Limnichthyes fasciatus (Collin and Collin 1997),the pipefish Corythoichthys paxtoni, and the round sardinellaSardinella aurita, which have higher corneal thickness in thecentral cornea than in the peripheral cornea (Collin andCollin 1988, 1995; Salem 2016). The sand burrower corneain particular has a thickened mucoid central area known asthe lenticle which is foundand sometimes a plane ofpolarization. All of these physical properties are detectable, in varying degrees, by the eyes of90% of all animal species. Ocular light detection depends on the conversion of light energy(a form of electromagnetic radiation) into an electrical signal, a chemical process calledphototransduction, which involves light-absorbing photopigments found in retinalphotoreceptors. Moreover, the production and emission of light by a living organism (biolumi-nescence) also occurs widely among animals, especially in the open sea, including fish,jellyfish, comb jellies, crustaceans, and mollusks, and in numerous insects. We believe thatfor most veterinary ophthalmologists, light is the closest thing to magic. Inquisitively, we usethe light of our instruments to examine and diagnose the very organ that transforms light intovision. Currently, we even use light, in the form of lasers or UV light, to treat severalconditions, such as glaucoma, retinal diseases, and corneal conditions. According to theCanadian poet Leonard Cohen: “There is a crack in everything. That’s how the light gets in.”Scientific discoveries made in the eyes of wild animals open the veterinary ophthalmologycrack just a little wider, and through it we get a better view not only of animal vision, but alsox Prefacehow the human eye works. For us ophthalmologists, light is all that is, was, or ever will be.Without sounding too pretentious, we sincerely hope that this book will bring someenlightenment, at least about this specific subject. We hope that this book brings our collegetogether to recapitulate those infrequent experiences over the past 50 years of our field, enablingus to fill the gaps left where limited or no experience was thought to have been obtained. As aresult, we hope that this book compels future growth in our field as we continue our fascination,care, and service for the animals of which we share our world.We must thank all those who have helped us in the production of this book. We havereceived an enormous amount of help from a very diverse group of authors and coauthors,coming from several different countries, possessing different mother tongues, educationbackgrounds, religions, and even political views, but all with two very importantcommonalities: (1) a fascination for the wild and exotic animal eye and (2) a devotion toveterinary ophthalmology. We may sound biased saying this, but the result has been excep-tional. We first would like to thank our fellow chapter authors for their tireless work. We alsothank our dear former and current mentors, colleagues, and friends who have contributed theirvast experiences, shared cases, and images, and have given advice.Fabiano would like to thank the other editors, especially Bret A. Moore, for having believedin him and embarked on this journey. Without Bret and Gil´s professionalism, dedication,enthusiasm, and expertise the result would certainly be inferior. This book has consumed aconsiderable amount of time in its creation (4 years)—long hours of organizational meetings,web meetings, countless phone calls, hundreds of e-mails exchanged, literature research andwriting, and lots of writing. All of these meant time away from our families. During this timeFabiano had a son (Giuseppe), one of our editors (Gil Ben-Shlomo) passed away, and we allwent through a difficult period in the COVID-19 pandemic. We faced the most serioussocioeconomic and health crisis of recent times. While we all had our struggles, the sense ofglobal community that emerged here, particularly among scientists, will certainly remain amemory to treasure. Therefore, Fabiano would like to dedicate his work on this book to hisfamily, especially Gabrielle Fornazari and Giuseppe Montiani. “There are darknesses in life andthere are lights, and you are one of the lights, the light of all lights.”—Bram Stoker.Bret would like to give his utmost thanks to his Father, “from whom I have been given thefreedom, resources, and intellectual ability to professionally explore His design throughscience, whereby my every attempt to further understand its beauty continually unveils withjoyful reverence the wonder of His creation, and that the existence of every living creature isnothing less than a gracious gift to His children, a most perfect design. It is with honor I canpresent this work to Him and the public in hopes that it displays to His people even a touch ofthe true splendor of His craftsmanship and brings Him, and only Him, glory.” He also wouldlike to specifically thank his mentors for their guidance and support while enabling him thefreedom to pursue such a project, as well as his twin Kelly Knickelbein for enduring hispreoccupation and entertaining his constant talking about random animals’ eyes. Additionally,his wonderful parents and sister, Mike, Tina, and Audrey Moore, deserve special attention fortheir love and support throughout both his childhood and adulthood that got him to where he istoday. Finally, Tara M. Czepiel, who every day provides more and more wisdom, support, andan encouraging presence that ultimately made the completion of this book possible.Finally, we express our deepest condolences on the recent death of Gil Ben-Shlomo. He willalways be remembered as a great professional and an even greater friend. His extraordinaryscientific knowledge as well as passion for veterinary ophthalmology was only surpassed by hisincredible positive influence and zest for life, especially when he was in the company of friendsand family.Curitiba, Brazil Fabiano Montiani-FerreiraGainesville, Florida, USA Bret A. MooreAmes, Iowa, USA Gil Ben-ShlomoPreface xiContentsPart I Early Photoreception, Invertebrates, and Fishes1 Evolution of Photoreception and the Eye . . . . . . . . . . . . . . . . . . . . . . . . . . . 3David L. Williams2 Ophthalmology of Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9Jenessa L. Gjeltema, Kate S. Freeman, and Gregory A. Lewbart3 Ophthalmology of Agnatha: Lampreys and Hagfish . . . . . . . . . . . . . . . . . . . 41David L. Williams4 Ophthalmology of Cartilaginous Fish: Skates, Rays, and Sharks . . . . . . . . . 47David Williams5 Ophthalmology of Osteichthyes: Bony Fish . . . . . . . . . . . . . . . . . . . . . . . . . 61Christine A. Parker-Graham, Brittany N. Stevens, June H. M. Ang, Esteban Soto,David L. Williams, Jennifer Kwok, and Bret A. MoorePart II Amphibia6 Introduction to Ophthalmology of Amphibia . . . . . . . . . . . . . . . . . . . . . . . . 107Jenessa L. Gjeltema7 Ophthalmology of Amphibia: Caecilians, Salamanders, Frogs, Toads, andRelatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121Christine Boss and Caryn E. PlummerPart III Reptilia8 Introduction to Ophthalmology of Reptilia . . . . . . . . . . . . . . . . . . . . . . . . . . 145Marco Masi, Paolo Selleri, and Bret A. Moore9 Ophthalmology of Rhynchocephalia: Tuatara . . . . . . . . . . . . . . . . . . . . . . . 153Kathryn Smith Fleming10 Ophthalmology of Gekkota: Geckos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167K. Tomo Wiggans and Bret A. Moore11 Ophthalmology of Scinciformata and Laterata: Skinks, Lizards, andRelatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183Kathryn Smith Fleming12 Ophthalmology of Anguimorpha and Iguania: Chameleons, Monitors,Dragons, Iguanas, and relatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205Kathryn Smith Flemingxiii13 Ophthalmology of Serpentes: Snakes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231Nicholas J. Millichamp14 Ophthalmology of Testudines: Turtles and Tortoises . . . . . . . . . . . . . . . . . . 271William M. BerkowskiJr. and Caryn E. Plummer15 Ophthalmology of Crocodilia: Alligators, Crocodiles, Caimans,posterior to the stroma and ante-rior to an iridescent layer. The lenticle is a unique adaptationfor corneal refraction; a feature not found in any other teleost.In addition to corneal refraction, it has been hypothesized thatthe sand burrower’s corneal adaptations might have arisendue to the need for extra turgor in the eye to support itslifestyle as a predator that ambushes prey whilst buried insand (Pettigrew and Collin 1995).Many diurnal species have lamellae in the corneal stromathat contain visible corneal nerves (Fig. 5.5) or corneal iri-descence. These lamellae are oriented in a single directionand often reflects incident light only coming from above thefish (Lythgoe, 1975). Some species are also able to changethe wavelength or amplitude of corneal iridescence inresponse to environmental light (Lythgoe and Shand, 1989).Corneal iridescence has been classified into 8 types of irides-cent layers based on structure and position on the cornea(Collin and Collin, 2001) and grossly can appear differentin both pattern and coloration (Fig. 5.6). This iridescenceoverlies the pupil and serves the function of concealing thefish’s eye to prey or predators. Corneal pigmentation in66 C. A. Parker-Graham et al.Fig. 5.4 The cornea of the sturgeon. (a) Gross photograph of sturgeoneye. (b) Slit lamp photograph showing a thin cornea. (c–d) Opticalcoherence tomography showing a shallow anterior chamber, particularlycentrally (d), and a thin cornea with relatively thick epithelial layer.(Courtesy of the University of California Davis School of VeterinaryMedicine Ophthalmology Service and Christopher J. Murphy)5 Ophthalmology of Osteichthyes: Bony Fish 67species such as the toadfish shows the ability to alter inresponse to changes in light intensity. Underlying diurnalrhythms play a role in corneal pigment changes, but experi-mental studies have shown the main cause for changes incorneal pigmentation to be environmental light. Pigmentchanges occur as pigments migrate from peripheral reservoirsinto chromatophores that extend centrally within the scleralcornea (Siebeck et al. 2003). Many functions have beenattributed to corneal filters in different species, includingultraviolet protection.Some teleost fish possess a Descemet’s membrane poste-rior to the corneal stroma (Smelser, 1962; Soules and Link,2005), while others either have an incomplete or completelyabsent Descemet’s membrane (Edelhauser and Siegesmund,1968). Supporting the cornea from underneath is the annularligament, which is comprised of a meshwork of connectivetissue containing proteoglycans such as keratocan andlumican (but interestingly neither collagen nor elastin) thatoccupies the iridocorneal angle (Jurk 2002; Chen et al. 2008).Pigments and glycogen content are often reported in thisligament and it runs circumferentially along the anteriorchamber (Asli et al. 2012). The annular ligament developsto maturity as the teleost eye matures through growth. In thezebrafish Danio rerio, the annular ligament can be histologi-cally differentiated from a mass of mesenchymal cells oncethe fish reaches one month of age. In the mature eye, theannular ligament forms an inverted “U” shape along the angledorsally, whereas ventrally, the ligament forms a funnelshape. It is also along the ventral border between the irisand the iridocorneal angle where aqueous drains into theiridocorneal canal, which then drains into the episcleral vas-culature. The annular ligament may appear acellular on his-tology, but electron microscopy has revealed small, irregularnuclei within annular ligament cells (Soules and Link, 2005).The true purpose of the annular ligament is unknown, but itmay have a secretory function. The corneal endothelium hasbeen reported to be missing in some teleost species. In spe-cies that do possess a corneal endothelium, it is attachedposteriorly to the annular ligament and is comprised ofmostly hexagonal or pentagonal cells, similar to that ofother vertebrates. Endothelial cell densities vary from speciesto species, but there does not appear to be a correlationbetween density and habitat or lifestyle (Collin and Collin1998b).The UveaThe iris is comprised of a heavily-pigmented anterior ecto-derm layer and a non-pigmented posterior layer. Iris pigmen-tation and pattern can vary significantly even amongindividuals of the same species. There is a thin stromabetween the iridal layers that contains blood vessels, melanin,and an anterior layer of guanophores. The stroma is anFig. 5.5 Corneal nerves in the stroma of a moray eel (Muraenidae). (Courtesy of David G. Heidemann)68 C. A. Parker-Graham et al.extension of the argentea and makes the iris iridescent. Thereare no muscle fibers present in the teleost iris and thereforepupillary light reflexes (PLR) are not observed (Jurk, 2002).The iris of fish is incredibly diverse and often ornate,causing pupil shape to vary widely, ranging from circularwith limited to no mobility, to slit-like pupils, to near endlesspossibilities of dorsal opercula (Fig. 5.7). While the iris playsa large role in moderating the level of light entering the eye inmost terrestrial vertebrates, most species of teleost fish haveimmobile pupils. As always, there are exceptions to this rule,Fig. 5.6 Corneal iridescence in Osteichthyes. (a) The eye of a tenchfish Tinca tinca, a freshwater teleost, showing no corneal iridescenceunlike that found in many saltwater species. Corneal iridescence can bedistributed uniformly across the cornea as in the map pufferfishArothron mappa (b), or more focally overlying pupil as in a differentpufferfish species (c). When pupil shape is not uniform, such as in thisunknown Stargazer species Uranoscopidae, whose horizontal tohorseshoe-shaped pupil matches the overlying pattern of corneal irides-cence (d). Radiating waves (e—Frogfish, Antennariidae), short linearspots (f—Scorpionfish, Scorpaenidae), tiny dots (g—Red Irish LordHemilepidotus hemilepidotus), and radiating linear stripes (h—Shortfinlionfish Dendrochirus brachypterus) are other possible patterns of iri-descence. i, j) Coloration can vary depending on species, angle orincidence, or ambient or type/intensity of the light source, as shown inthis balloonfish species. (a—Used with permission from Kletr,Shutterstock.com. b—Used with permission from Ethan Daniels,Shutterstock.com. g—Used with permission from Nature PictureLibrary, Alamy Stock Photo. h—Used with permission from scubaluna,Shutterstock.com. c, d, e, f, i, j—Courtesy of David G. Heidemann)5 Ophthalmology of Osteichthyes: Bony Fish 69http://shutterstock.comhttp://shutterstock.comhttp://shutterstock.comFig. 5.7 Iris morphology and pupil shape in Osteichthyes. (a) Anacircular pupil in a seahorse that is common amongst saltwater fish,and (b, c) a dorsal, horizontally oriented slit-like pupil in an unknowneel species. Dorsal opercula can vary from a single appendage (d—Stargazer, species unknown), to a bi-lobed appendage (e—Devilscorpionfish Scorpaenopsis diabolus), to multilobed appendages thatcan be single stalks (f—Longsnout flathead Thysanophrys chiltonae) orhave numerous branches (g—Crocodilefish Cymbacephalus beauforti).(a, b, c, d—Courtesy of David G. Heidemann. e—Used with permissionby Magnus Lundgren, Wild Wonders of China, Nature Picture Library.f—Used with permission from Scubazoo, Alamy Stock Photo. g—Usedwith permission from Alex Mustard, Nature Picture Library, SciencePhoto Library)70 C. A. Parker-Graham et al.including the Amazon sailfin armored catfishPterygoplichthys pardalis. Under light conditions, thisteleost’s round pupil transforms into a crescent-shapedpupil due to an irideal flap that grows dorsoventrally toobscure the central pupil. Pupillary constriction occurs rela-tively quickly, but subsequent dilation takes several minutesto complete, which is much longer than terrestrial vertebratessuch as humans, which takemere seconds for pupillaryre-dilation. This is because lower vertebrates only possessan iris sphincter muscle and no iris dilator muscle; therefore,pupil dilation must only occur passively (Douglas et al.2002). Pupillary responses tend to be slow in teleost speciesand a consensual response has been found to be present indifferent degrees in different species. It has also been notedthat species of teleost that possess pupillary movements tendto be eels as well as dorsoventrally flattened fish that spendmost of their time living in substrate. This is likely due to thefact that in addition to modulating light flux incident on theretina, substrate-dwelling species also rely on pupillary con-striction to conceal their pupils with irises that allow blendinto their substrates for camouflage (Douglas et al. 1998). Astudy on the goosefish Lophius piscatorius and the toadfishOpsanus tau found that iris constriction can be induced bycholinergic or adrenergic agonists, and that teleost irises areprimarily controlled by cholinergic innervation (Rubin andNolte 1981).Another feature to note is the fact that many predatoryteleost pupils are not symmetrically round like that of terres-trial vertebrates. The pupil of species such as the lingcodOphiodon elongatus appears slightly pointed rostrally dueto the presence of a nasal aphakic space (Fig. 5.8). Althoughthe nasal aphakic space is most common, some species suchas the common archerfish Toxotes chatareus may have tem-poral aphakic spaces too. The aphakic space is particularlyimportant in predatory species because it allows more light toenter the eye at oblique angles rostrally. This means thatpredatory fish with nasal aphakic spaces have binocularvision rostrally, which improves their ability to locate prey.The functionality of the aphakic space corresponds to regionsof the peripheral retina containing high photoreceptor den-sity, much like the fovea in humans (Gagnon et al. 2016). Indeep-sea species, aphakic spaces also function to increaseretinal illumination (Locket 1980).In many teleost species the ciliary body is rudimentary andmerges directly with the iris. The choroid is comprised of theargentea, choroidal gland, and falciform process. The choroidis responsible for the majority of the nutrition and immunefunction of the eye. The choroid does not have a true tapetuminstead light is reflected by the argentea, a silver-yellowreflective layer comprised of guanophores; the argentea isthought to also function in camouflage for larval fish. Thechoroidal gland (also known as the choroidal rete) is ahorseshoe-shaped, densely packed collection of capillariessurrounding the optic nerve. Countercurrent flow throughthese capillaries concentrates oxygen in oxygen-poor watersand allows a high oxygen tension to be delivered to thechoroid. In species with a pseudobranch (a reduced first gillarch that no longer functions in a respiratory capacity butmay be important for water oxygen level sensing) there is adirect connection between the pseudobranch and the choroi-dal gland. The falciform process is a highly vascular ridge ofchoroidal tissue that protrudes through the retina. It functionssimilarly to the pectin in avian eyes and the cone in reptilianeyes to nourish the avascular retina.Refraction and Lens AnatomyTerrestrial animals have an air–cornea interface throughwhich refraction can occur. Fish corneas are flat, and therefractive index of water is nearly equal to the refractiveindex of the curved corneal surface seen in terrestrial animals.Corneal surface irregularities are common in fish and whilesuch irregularities would result in astigmatism in terrestrialanimals this effect is negated by the cornea–water interfacefor fish. Since the refractive index of teleost corneas is nearlyequal to that of the water they inhabit, the lens is the only sitethrough which refraction can occur in most teleost species(Russell, 1988). The refractive error of fish lenses has beenmeasured to be higher than that of any other vertebrate(~1.69) (Williams 2012).In most teleost species, the lens is spherical. Because ofthe structure and size of the lens, it is often possible to see theanterior aspect of the lens protruding through the pupillaryaperture in normal animals (Fig. 5.9). The fish lens is denseand spherical to slightly elliptical and is comprised of anucleus, a cortex, and a capsule, all of which are histologi-cally similar to their mammalian counterparts. The densityand shape make deformation of the lens for accommodationimpossible, so fish rely on changing the position of the lensfor accommodation. Fish alter the anterior-posterior locationof the lens relative to the pupil to change their plane of focus.The lens is suspended in the pupillary aperture by a dorsally-located suspensory ligament and a ventrally-located retractorlentis muscle. Contraction of the retractor lentis musclefacilitates pendulous movement of the lens posteriorlytoward the retina, which reduces the focal length of vision(Andison and Sivak 1994) (Fig. 5.8c). Accommodative abil-ity is based on the feeding habits of a given species, andsight-based predatory fish have some of the bestaccommodative ability among all vertebrates (Jurk 2002).Young fish often lack the ability to accommodate throughlens movement. During larval development, theMatthiessen’s ratio (ratio of the distance from center of lens5 Ophthalmology of Osteichthyes: Bony Fish 71to retina to lens radius) of the eye also tends to be high. Larvalfish compensate for this by having high focal ratios in theirlenses to allow them to focus images at different distances(Shand et al. 1999).The teleost lens serves many roles in different species. Insome deep-sea species, the lens is pigmented and acts as alight filter, for instance in the bright yellow lens of thestoplight loosejaw Malacosteus niger, which allows it toFig. 5.8 Aphakic space in Osteichthyes fish. (a) A blue-spottedcornetfish Fistularia commersonii with a large nasal aphakic crescent.(b) A smaller nasal aphakic crescent in a scorpionfish species. (c) Adorsal aphakic crescent in two different fish (species unknown). Thesefish are exhibiting different degrees of lens retraction, being great in thefish on the right, causing an increase in the width of the aphakic crescent.(a, b—Courtesy of David G. Heidemann. c—Used with permissionfrom neiljohn, Alamy Stock Photo)72 C. A. Parker-Graham et al.discriminate between red bioluminescence from blue day-light (Somiya 1982) (Fig. 5.10). In the Mexican tetra Astya-nax mexicanus, a blind cave fish, the lens plays a role in eyedegeneration. In the cave fish embryo, eye formation isinitiated and then stops and degenerates before eye develop-ment completes. Transplantation of the embryonic cave fishlens into the developing eye of a surface fish has been foundto result in a non-visual, regressed eye (Yamamoto andJeffery, 2000).A group of deep-sea teleosts collectively known aspearleyes (family Scopelarchidae) have dorsally directedtubular eyes that are also able to see in front and belowthem (Fig. 5.10). The globe is a slightly oval shape and hasa spherical lens situated dorsally. The main retina is situatedin the ventral fundus and receives light entering from over-head; however, there is also an accessory retina situated alongthe caudal fundus. Light received by this accessory retina isrefracted through a transparent lens pad that overlies anaphakic gap between the lens and the iris. In the childishpearleye Benthalbella infans, the lens pad attaches dorsally tothe cornea at the level of the center of the lens and attachesventrally to the iris. Light coming from the front or below thefish thus gets refracted by the lens pad and the lens to bedetected by the accessory retina (Locket 2000).Unlike other species, the sand burrower has a flattenedlens that contributes an average optical power of 550D (60%ofthe total optical power of the eye), while the corneacontributes an average of 200D refractive power (Pettigrewand Collin 1995). The optical morphology of this species isconsidered an example of convergent evolution when onecompares it to the chameleon because both of these specieshave corneas that offer refraction, accommodation, andreduced lens power. Corneal accommodation is achievedthrough the striated cornealis muscle which inserts onto thecorneal stroma. Corneal accommodation is achieved rapidlyat—720D or 25% of the total ocular power per second. Thisis opposed to other teleost fish that rely on lens movement toachieve around 10D or 5% of their total ocular power persecond in accommodation (Tamura andWisby 1963). At rest,the sand burrower cornea is at a highly myopic state (180D)Fig. 5.9 The anterior chamber depth and lens position of fish. (a) Thetiny mosquitofish Gambusia affinis has a relatively flatter anterior lenssurface and minimal protrusion into the shallow anterior chamber. (b–d)A scorpionfish species (Scorpaenidae) displays large lenses with slightprotrusion into the anterior chamber. Black arrows pointing outwardfrom the eye are labeling the iris margin, whereas black arrows pointinginward are labeling the anterior lens capsule. White arrows denote theiris. (e) A porcupinefish species (Diodontidae) and (f) a moray eelspecies (Muraenidae) show relatively smaller, more circular lenseswhich prominently protrude through the pupil and into the anteriorchamber. The white arrow is highlighting the posterior cornea. (a—Courtesy of Bret A. Moore. b–f—Courtesy of David G. Heidemann)5 Ophthalmology of Osteichthyes: Bony Fish 73and contraction of the cornealis muscle flattens the curve ofthe cornea and causes a reduction in power. The ability tomanually adjust focus is combined with the increased sepa-ration between the nodal point and axis of rotation of the eyedue to the eye’s morphology. A magnified retinal image istherefore produced (myopic at rest), while small rotations ofthe independently moveable eyes provide monocular parallaximages of prey. It has been reported that predation on thesand burrower is very low when this species was observed inits natural habitat. A pigmented epithelium overlying the eyesprovides further camouflage against the background of sandfrom which its eyes protrude while it ambushes prey. Just likethe chameleon, the sand burrower’s ophthalmological anat-omy gives it the advantage of becoming an effective ambushhunter, whilst also allowing it to avoid predation (Pettigrewet al. 1999; Land 1999).Vision above and below water is required in species suchas the flying fish (family Exocoetidae) and the four-eyed fishAnableps anableps. The four-eyed fish has half of its eyesprotruding from the water’s surface and is able to look aboveand below the waterline at the same time. The dorsal cornea isflatter with a thick epithelium of over >20 cell layers. Thedorsal corneal stroma is thickest at the center to allow forcorneal refraction and is protected from UV irradiation anddesiccation by high glycogen content (Swamynathan et al.2003). The flying fish Cypselurus heterurus cornea isorganized into a pyramidal shape with the point at the centerof the cornea. This corneal design allows for refraction thatresults in emmetropia in air but results in slight hyperopia inwater (Baylor 1967).The Retina and PhotoreceptionIn order of increasing depth, the teleost retina is composed ofa Bruch’s membrane, pigment epithelium, photoreceptorlayer, outer limiting membrane, outer nuclear layer, outerplexiform layer, inner nuclear layer, inner plexiform layer,Fig. 5.10 The tubular eyes anddorsally positioned sphericallenses in (a) the Shortfin pearleyeScopelarchus analis and (b) theMirrorbelly Monacoa grimaldii.Note the yellow lenses (a) thatincreased the discriminativeability of bioluminescence. (Usedwith permission from DanteFenolio, Science Photo Library)74 C. A. Parker-Graham et al.ganglion cell layer, and nerve fiber layer resting on top of aninner limiting membrane. Many species also possess a reflec-tive retinal tapetum (Waser and Heisler 2005). The commonancestor of teleost fishes likely had a thin retina with nochoroid rete mirabile. Throughout teleostean evolution,larger eyes have been accompanied with thicker retinae.The anatomy of retinal blood supply varies between choroidrete mirabile, preretinal capillaries, and intraretinal capillaries(Damsgaard et al. 2019). Many teleost species have avascularretinae and they achieve sufficient oxygenation of the retinathrough the Root effect of select types of hemoglobin.Through the Root effect, intraocular pO2 increases as adecrease in pH causes a decrease in oxygen affinity andcarrying capacity of these specialized hemoglobin molecules(Root and Irving 1943; Waser and Heisler 2005). Evolution-arily, a high magnitude in the Root effect has been associatedwith the loss of preretinal or intraretinal capillaries and theevolution of a choroid rete mirabile instead. The loss ofpreretinal capillaries provides enhanced vision due toreduced light scattering caused by preretinal capillaries.(Damsgaard et al. 2019). The choroid rete mirabile is ahorseshoe-shaped structure of packed parallel arterial andvenous capillaries that radiate around the optic nerve in thechoroid. It is supplied mainly by the ophthalmic artery whichbranches out from the pseudobranch but is also supplied to alesser extent by the retinal artery, which arises from theinternal carotid and also supplies the optic nerve, extraocularmuscles, and periorbital fat. Deoxygenated blood is drainedinto the ophthalmic and retinal veins (Barnett 1951). In theventral fundus of species such as the rainbow troutOncorhynchus mykiss, a structure known as the falciformprocess protrudes anteriorly along the embryonic fissure ofthe globe and is part of the choroid (Fig. 5.11). This structureis vascularized by the rete mirabile and at least four differenttypes have been found in various species based on anatomicalstructure (Hanyu 1959). Although this system provides thebenefit of oxygenating an avascular retina, it also predisposesto hypoxia under general acidosis as oxygen loading in thegills may be hampered. Coincidentally, it is also through theevolution of the Root effect in hemoglobin that allowed thedevelopment of oxygen secretion into the swim bladder evenagainst high hydrostatic pressure, leading to some teleostgroups moving into deep-sea habitats (Berenbrink 2007).Additionally, Antarctic fishes have been found to have anincreased anatomical capacity to supply blood to the retinadue to reduced oxygen-carrying capacity of the blood(Wujcik et al. 2007).Species such as topminnows Fundulus spp. and zebrafishDanio rerio that do not possess falciform processes insteadhave hyaloid vessels (preretinal vessels) at the vitreo-retinointerface. These vessels serve similar functions as that of theretinal artery (Copeland and Eugene 1974). During develop-ment, hyaloid vessels in zebrafish transiently initially sur-round the growing lens before attaching to the surface ofthe fundus. This pattern of developmental change in hyaloidvascular arrangement is also seen in many mammals, whichFig. 5.11 Gross hemisection of the eye of a yellowfin tuna Thunnus albacares displaying the falciform process. (Courtesy of Richard R. Dubielzig)5 Ophthalmology of Osteichthyes: Bony Fish 75is why this species is used as a model for mammalian retinalvasculature diseases such as persistent fetal vasculature(Alvarez et al. 2007). Exceptions to the common anatomicalfeature of a rete mirabile are channichthyids—a group ofhemoglobin-less Antarctic fish that carry oxygen in solutionin the blood and have hyaloid vessels that drain into acircumferential annular vein (Eastman and Lannoo 2004).In addition to photoreception by the eyes, the pineal glanddeserves to be mentioned forits role in extraocular photore-ception. The pineal gland, also referred to as the pinealapparatus, has long been described in many teleost speciesas an organ that directs phototactic responses as well asphysiological changes such as pigment distribution inchromatophores (Hoar 1955; Hafeez and Quay 1970). Inthe bluefin tuna Thunnus thynnus, the pineal apparatus issituated on the dorsomedial region of the skull through thepineal foramen and is composed of a pineal window coveredwith translucent dermal tissue, leading to a pineal dome andpineal tube leading to the pineal area of the brain (Rivas1953). The pineal organ was found in the bagrid catfishHemibagrus nemurus to be functional in larvae, with lens-like tissue that ossifies as larvae mature to form the pinealwindow. The pineal apparatus plays a role in negative photo-taxis in these larvae (Rahmah et al. 2013).Color VisionThe mammalian species which form the majority of animalsseen by veterinary ophthalmologists are dichromats whileprimates as humans are trichromats. Fish have the potentialfor detecting four different ranges of visual spectra, so beingtetrachromats a discussion of color vision in these species iswell worth pursuing. Having said that, fish inhabit a multi-tude of habitats from the clear waters of the reef to thedarkness of the deep sea and species in different nicheshave different adaptations for color vision some losing thediversity of cones while others have tuned their spectralsensitivity to suit their specific environmental niche. Thephototransduction cascade is activated when light enteringthe eye induces a conformational change in a retinalphotopigment. In cone photopigments, this conformationalchange involves a cis-trans isomerization of a chromophore11-cis-retinal. Within the repertoire of opsins in the animalkingdom, vertebrate visual opsins encompass the rodphotopigment RH1 [rhodopsin 1 (RH1)] as well as the fourcone visual opsins LWS/MWS (long-wavelength-sensitive),SWS1 (short-wave-sensitive; UV/violet-sensitive), SWS2(blue-sensitive), and RH2 (green-sensitive) (Imamoto andShichida 2014). Not all species have the same types ofphotopigment and even when regarding the same type ofphotopigment, spectral tuning (changes in amino acidsequences modulating chromophore structure) can result inphotopigments that are able to perceive slightly differentwavelengths of light. As an example, the RH1 photopigmentis rod opsin common in all vertebrates with vision, yet evenlooking at this photopigment alone, the wavelengths of lightλmax that this pigment absorbs in deep-sea, intermediate andsurface species are 480–485, 490–495, and 500–510 nm,respectively (Yokoyama 2008). While most vertebrates useA1 retinal as a chromophore in rhodopsin molecules, somefish species instead have 3,4-dehydroretinal (A2 retinal) inporphyropsin molecules, which results in red-shifted absorp-tion (Wald 1953).In the deep sea, the high requirement for sensitivity tolight perception (scotopic vision) means that most specieshave simplex retinae comprising only of rods (Locket 1980;Fröhlich et al. 1995; Wagner et al. 1998). Some species suchas the deep-sea pearl eye Scopelarchus analis appear to havecolor vision, as was found in a study by Pointer et al. (2007)who revealed the presence of a retinal cone pigment [rhodop-sin 2 (RH2)]. Color vision is perhaps retained in S. analisbecause this species is known to live in shallower waterswhile in the juvenile stage, before migrating into the deepsea as they mature into adults. Another interesting deep-seaspecies with a surprising adaptation for color vision is thepearlsideMaurolicus spp., which feeds near the surface of thesea during dusk and dawn in mesopic light levels. Thisspecies has a small number of rods and mostly rod-liketransmuted cones that contain a cone opsin but have themorphological characteristics of rods. This acts as an optimi-zation of vision and an alternative to having rods and coneswhich both do not work best in dim light. It is hypothesizedthat evolutionarily, cone photoreceptors in this species trans-muted morphologically to resemble rods (de Busserolleset al. 2017).Rather than having cones in their retinae, some deep-seafish have been found to use widely variable rod opsins, asopposed to the single RH1 rod opsin that most vertebratesuse. To adapt to the dark deep-sea environment, it wouldmake sense for these species to also have anatomicaladaptations such as large eyes, dilated pupils, very long rodcells, multibank retinae (rods placed in layers on top of eachother), and a reflective cell layer (García et al. 2017). In astudy by Musilova et al. (2019), the silver spinyfin Diretmusargenteus was found to have the highest number of visualopsins in vertebrates, possessing 38 RH1 genes, 14 of whichare expressed in adulthood. Species such as D. argenteuswith rod receptors of different spectral sensitivities alsohave a yellow pigment in the retina that absorb primarily inthe blue and near-UV and acts as a spectral filter and mayfurther enhance color discrimination and contrast (Dentonet al. 1989). The precise purpose of possessing so many rodopsins in these species cannot be verified without a behav-ioral study, however the wide range of wavelengths that thisexpanded RH1 repertoire can theoretically allow differently76 C. A. Parker-Graham et al.tuned photopigments to detect not only bioluminescencefrom the dark, but also different types of bioluminescence,which can contribute to prey capture or interspecies interac-tion. Having such a system with many photopigments at thefish’s disposal may also aid in optimizing vision in differentdevelopmental stages, as suggested by Marshall et al. (2015).Widely used in research, zebrafish Danio rerio are one ofthe most studied species of fish (Arunachalam et al. 2013).These minnows originate from clear freshwater habitats inIndia and from the larval stage are heavily reliant on visionfor capturing microorganism prey (Patterson et al. 2013).According to a study by Zimmermann et al. (2018), thelarva’s eye takes up almost a quarter of its body volumeand half of its CNS neurons are located in the eye. Theyhave four cone types expressing opsins which are longwavelength-sensitive (LWS; 548 nm), middle wavelength-sensitive (MWS; 467 nm), short wavelength-sensitive (SWS;411 nm), and UV-sensitive (UVS; 365 nm). Tetrachromaticvision is present throughout the lower visual field and towardthe visual horizon, where most chromatic content can be seenby the fish, with a higher concentration of UV-sensitive opsinexpressed in the area temporalis, which is the caudo-ventralarea of the retina contributing to the fish’s “strike zone”(Yoshimatsu et al. 2019; Schmitt and Dowling 1999). UVsensitivity in retinal cones aids in the detection of planktonicprey such as paramecia that readily scatter UV light. Thisability is also seen in several other fish species such as therainbow trout and Malawi cichlid (Jordan et al. 2004;Flamarique, 2013). Rods in the zebrafish eye are exclusivelyused for capturing photons from Snell’s window directlyabove and light reflections from the ground directly beneaththe fish.Color vision does not always include the full visiblespectrum in fish. The largemouth bass Micropterussalmoides, a large freshwater top predator from North Amer-ica, has dichromatic vision as they only have two types ofcones: green-sensitive single cones and red-sensitive twincones, also known as double cones (Mitchem et al. 2019).In behavioral trials, the bass had difficulty differentiatingbetween chartreuse yellow and white and between blue,green and black. Red appeared to be the easiest color forthe bass to differentiate from other colors. Not only isM. salmoides strongly able to distinguish red colors, thisspecies is also considered to have a behavioral preferencetoward the color red, as red lures appear to be most effectivewhen fishingfor this species (Kawamura and Kishimoto2002). A preference for red colors has been seen in otherpredatory fish species as well. Zebrafish appear to show aninnate preference toward red-colored feed, even if they havebeen conditioned by being fed feed of other colors since birth(Spence and Smith 2008). Commercial fish feed given toAtlantic salmon Salmo salar in aquaculture are always of abright orange-red color, as they have highest feeding rates forfeed of a red color (Clarke et al. 1985). This common bias inchoosing red-colored feed is due to this color being indicativeof high carotenoid content, an important part of fish health(Tacon 1981; Torrissen et al. 1995; Craik 1985).Fish often have very organized retinae, with cells arrangedinto a retinal mosaic. Metriaclima benetos, a species of cich-lid from Lake Malawi in Africa that is highly visual, hastrichromatic vision and a square retinal mosaic organizedwith a single (SWS opsin) cone surrounded by four doublecones that express RH2B (blue-green) and RH2A (green)pigments. Colors are differentiated by color opponency,where spectral differences between different double conesare registered by ganglion cells to generate the color per-ceived by the fish (Escobar-Camacho et al. 2017). A study ofM. zebra, a closely related species also from Lake Malawi,showed that there is co-expression of different opsins on thesame cone cells. The distribution of cells exhibiting opsinco-expression is also varied across the retina, with reducedco-expression in the area centralis, the region within theretina used for high acuity vision. Co-expression in cichlidshas also been shown to change with changes to environmen-tal light during its life (Dalton et al. 2015). Dalton et al.(2017) have further shown that co-expression may improvethe fishes’ abilities to detect dark objects contrasted againstbright backgrounds, but may hinder color discrimination,hence the preferential placement of retinal cells showingopsin co-expression in the areas contributing to peripheralvision. This structural adaptation of the cichlid retina presentsas an example of a fine balance between quick spectral tuningand vision acuity. The strong ability to differentiate colorscomes in handy for these cichlids because not only do theseomnivores forage for a wide range of feed including algaeand zooplankton (McKaye et al.1983), they are also highlydependent on visual cues for sexual selection and subse-quently larva rearing (Pauers et al. 2008; Jordan et al. 2003).Returning to oceanic fishes, another group of species towhich color vision is highly important are reef fishes. Dam-selfish (lemon damselfish Pomacentrus moluccensis &ambon damselfish Pomacentrus amboinensis) andcardinalfish (yellow-striped cardinalfish Ostorhinchuscyanosoma) express five cone opsins including theUV-sensitive SWS1 and one rod opsin. These three specieshave been found to be able to alter opsin gene expressionwithin months or even weeks to adjust to changes in environ-mental light. Only cone opsin genes were found to vary inexpression to match the levels of different light spectrumsand intensities, so long wavelength-sensitive opsins areexpressed more in environments with reduced short-wavelength light. Rhodopsin levels, on the other hand, stayedunchanged regardless of light differences. Additionally,cardinalfish has been found to have a high baseline expres-sion of rhodopsin (RH1 ~ 90%), while damselfish rhodopsinis expressed in around 60% of the retina. This relates to the5 Ophthalmology of Osteichthyes: Bony Fish 77ecology of these fish, as the nocturnal cardinalfish benefitsmore from low light-sensitive rhodopsin, while the diurnaldamselfish would not need highly light-sensitive vision(Luehrmann et al. 2018). UV-sensitive opsins are importantto many small reef fish as UV-reflective markings such asfacial markings allow for conspecific communication andheterospecific recognition, whilst still being invisible toUV-blind predator fish (Partridge and Cuthill 2010;Schluessel et al. 2014).As exampled above, opsin expression in the retina canchange to fit with the fish’s survival requirements in differentlife stages. The Pacific pink salmon Oncorhynchusgorbuscha shows a permanent change in opsin expressionin its single cones from UV-sensitive opsins to blue-sensitiveopsin as it matures and has increased need for blue lightperception over UV perception. This is because this speciespredates on zooplankton as freshwater fry before graduallytransitioning onto predating small fish while migrating intodeeper oceanic waters as they grow into adults (Cheng et al.2004). Hormonal changes can also cause changes in retinalopsin expression as in the sexually mature male three-spinedsticklebacks Gasterosteus aculeatus, which becomes moresensitive to red light with increased lws mRNA levels duringthe summer breeding season (long photoperiods). Theincrease in red light sensitivity is regulated by levels ofcirculating androgen and aids the discernment of mates, asincreased red colorations and sexual dimorphism in breedingmales and females are observed in mate selection (Shao et al.2014). In the orangethroat darter Etheostoma spectabile,color vision plays a role in sexual selection only in males asthey compete against conspecific rivals (Zhou et al. 2015).In highly visual fish species, color often serves the func-tion of communication, or the lack thereof in the case ofcamouflage. Regarding camouflage, the reflectance of thefish’s body color against its environment as well as thecolor perception of the potential predator must be considered.Reef fish readily increase the redness of their coloration in thenight, as red appears almost as black through the blue filteredlight in the sea due to spectral attenuation (Marshall et al.2018). Unlike terrestrial animals, most aquatic interactions donot require long distance vision, as water allows for a shortervisual range than air. Resolving powers of fish vision istypically 10� less acute than that of humans (Collins andPettigrew 1989), so reef fish often possess bright patterns andbody coloration among other phenotypical adaptations tocamouflage against the colors of coral and the ocean (Mar-shall 2000).While color vision has been helpful to the survival ofmany fish species throughout evolution, anthropogeniceffects on the environment have negatively affected colorrecognition in fish. Light pollution in coastal areas or fromships have been found to disrupt lunar patterns perceived byfish (Davies et al. 2013; Gaston et al. 2013), leading todownstream changes in physiological functions such asspawning timing (Duston and Bromage 1986). Excessivelight also hinder nocturnal fish that forage or hunt under thecover of darkness, while increased predation has been seenwhen small fish congregate under artificial light during thenight (Davies et al. 2014). The dependence of reef fish onenvironmental colors for camouflage also means that coralbleaching has resulted in less cover for many of these species(Kaplan 2009). Water pollution causing increase turbidity hasled to selective increase in fish that are more able to adapt toturbid waters (Schmidt 2001), while chemical pollution hasbeen shown to cause ophthalmological impairments such asreduced retinal response capacity due to disruption of GABAreceptor function in acidified water (Chung et al. 2014).Fish show many adaptations that help them differentiatecolors, from retinal pigments that act as spectral filters toalterations in opsin expression in tune with environmentallight changes. Colors are also crucial in many fish species forcommunication and behavior. As our knowledge on newspecies continue to grow, future research carries great poten-tial as new discoveries inform on natural processes as well asthe effects of human action on fish.Ophthalmic ExaminationThe first part of any fish diagnostic workup is compilingacomplete history, not only for the individual patient but forthe entire system. A thorough history will include informa-tion about the population of the system, water quality of thesystem, and specifics about the clinical signs of the patient; alist of suggested questions is provided in Box 5.1. Beforehandling the patient, one should perform a hands-off obser-vation of how the fish navigates its transport container andinteracts with its tank mates (if any). This often requirespatience because fish will swim with their affected eyeaway from the observer and may hide in any providedshelters. The authors find it useful to ask owners to bringvideos of any abnormal behavior that they are observing intheir fish from home as this gives insight to how the fishbehaves in a familiar environment. Fish with ocular diseasemay isolate themselves from their tank mates, may haveabrasions from conspecific trauma or colliding with tankfurnishings, spend more time hiding in shelters and substratethan normal, may be thin or underconditioned, and may bedarker in color (pigmentation is under neuroendocrinecontrol).Anesthesia should be considered for fish patients whenperforming a routine ophthalmic exam. The authors anesthe-tize any fish that is examined out of water. Anesthesia is avaluable tool to facilitate a safe exam and can significantlyreduce patient stress during handling. Even seemingly-smallfish can be very strong, they can easily injure human handlers78 C. A. Parker-Graham et al.and themselves by jumping out of restraint during an exam.Recent literature (Neiffer 2007; Neiffer and Stamper 2009;Sneddon 2012) provides a thorough review of fish anestheticoptions and procedures. When planning your examination,ensure that the owners or keepers will be bringing enoughtank water to mix an anesthetic bath and to have a freshwaterrecovery bath available. A small bubbler and air stone isgenerally sufficient to aerate the anesthetic and recoverybaths for an exam. For longer procedures, one may have toconsider accumulation of nitrogenous waste and maintenanceof the temperature of the bath as well.Box 5.1 Important Questions Regarding History WhenPerforming Ophthalmic Examinations in FishWhat are the patient’s current clinical signs? What isthe duration of the current clinical signs? Have theclinical signs changed since their onset?Are there other fish in the tank? If so, are anyaffected with similar clinical signs? Are there fish inthe tank affected with other clinical signs?Have the owners noticed behavioral changes such asisolation, piping, flashing, buoyancy disorder, irregularswimming, etc.?When and where was the affected fish obtained?Where were other animals in the system obtained?Have there been any recent additions (animals,plants, live rock) to the system?Is there a quarantine procedure in place beforeadding new animals to the system?What size in the tank? How many fish are in thesystem? What species are the other fish in the system?Are there any invertebrates, amphibians, or otheranimals in the system?What and how often are the fish fed? Do the ownersnote any aggression around feeding time?What type of filtration system is in place in thesystem? How often is the filtration system serviced?How often are water changes performed on thesystem? How much water is changed at once? How isfree water treated before being added to the system?Do the owners routinely test water quality? If so,what parameters do they test and by what method?Have the owners administered any other treatmentsto the system prior to their visit?For outdoor ponds it’s also important to gatherinformation regarding any potential sources of run off(lawns, plants, swimming pools, etc.) that may intro-duce chemicals into the water and get an idea of tem-perature changes that the system may have recentlybeen exposed to.Fish have an external mucous coat, or “slime coat,” that isproduced by goblet cells within the epithelium and containspeptides and molecular compounds important for localimmune function; the mucous coat also serves as an impor-tant physical barrier against pathogens and parasites andfactors heavily in osmoregulation. Inappropriate fishhandling (i.e., excessive time netting, abrasive exam surfaces,excessive handling) and desiccation can compromise themucous coat and make fish more susceptible to disease andosmoregulatory dysfunction. Furthermore, fish with oculardisease often present with exophthalmia, buphthalmia orcorneal ulceration and struggling during capture and handlingcan often lead to further damage to already compromisedocular structures. Abrasive exam surfaces should be avoided,the authors prefer chamois cloths soaked in the fish’sanesthetic-free transport water and wet powder-free nitrilegloves to protect fish against abrasive injury during exam.Absorptive cage pads with the smooth plastic side up can alsobe used. For species with rough skin (i.e., elasmobranchs),armor plates (i.e. sturgeon), or spines, neoprene diving glovesor Kevlar bite gloves may be used for an additional layer ofhandler protection. For human safety it is also important to befamiliar with the species that is being examined, particularlyin relation to the presence of any poisonous spines or pro-pensity to bite.Because so many ocular presentations are related to sys-temic disease a full workup is indicated in many patients. Afull physical exam with skin scrapes and gill biopsies shouldbe performed for all ill fish patients. Traditional radiographycan provide important insight to the musculoskeletal system,gastrointestinal tract, and swim bladder. In regard to ocularpresentations radiography can be helpful to delineatebetween gas and soft tissue opacities in the retrobulbarspace (Fig. 5.12a). Anesthetized fish can be safely kept outof water for three to five minutes, which means that fish mayneed to be returned to anesthetic water in between radiogra-phy shots. Positioning for lateral projections is straightfor-ward in most species and soft, closed-cell foam pads can beused to position dorsoventral projections. Radiography platesshould be wrapped in plastic to protect against water damage.It is also important to keep in mind that excessive water of theplate can obscure structures and make radiograph interpreta-tion difficult.Ultrasonography is also extremely useful for examinationof ocular disease of fish. Because patients are in an aquaticenvironment and water acts as a conductive agent, the ultra-sound probe can be held several centimeters away from theocular surface while scanning (Fig. 5.12b). If the patient istolerant, this approach may even allow the practitioner toperform ocular ultrasound without necessitating the use ofgeneral anesthesia; though in the authors’ experience, general5 Ophthalmology of Osteichthyes: Bony Fish 79anesthesia allows for easier manipulation of the patient whichfacilitates optimal imaging of the eye. Similar to radiology,ocular ultrasound can be used to differentiate between gasand soft tissue in the retrobulbar space. It can also be used toobserve for signs of retinal detachment or disease, changes tothe lens or for visualization of soft tissue material such asfibrin or hemorrhage in the posterior chamber as is commonlyseen after ocular trauma (Fig. 5.12c). If the cornea is opaquedue to severe corneal edema ultrasonography can be used toevaluate the anterior chamber. Finally, ultrasonography canalso be used to help facilitate ultrasound-guided fine needleaspiration of the retrobulbar space or posterior chamber if it isdeemed clinically indicated.Blood work is often useful to identify underlying causes ofophthalmic disease and may be necessary in some cases.Basic fish blood work includes a complete blood count andchemistry, but blood cultures are important in many cases aswell. There are published reference intervals for some com-monly kept ornamental species.The caudal hemal arch is themost commonly used venipuncture site in teleosts and cangenerally be accessed by either a ventral or lateral approach.When performing venipuncture, it is important to penetratethe skin between scales rather than puncturing through ascale, which can be painful and induce ulcer formation.Ethylenediaminetetraacetic acid (EDTA) anticoagulants lyseerythrocytes of many fish species, therefore heparin is thepreferred anticoagulant (Noga 2010). With regard to bloodcultures it is important to keep in mind that aquatic bacterialpathogens grow at temperatures generally lower than mam-malian pathogens; it is important to confirm with your refer-ence lab that you are submitting a culture sample from a fishpatient and that the lab has the capability to properly incubatethese samples.Although a slit lamp biomicroscope is preferred for athorough ocular examination, a standard ophthalmoscopecan often be sufficient. Because of the size of the eye andthe shape of the iris, fundic exams are often unrewarding.Both applanation and rebound tonometry have been used infish, the limiting factor is often the size of the cornea; manypet fish examined are too small for applanation tonometry. Inthe brook trout Salvelinus fontinalis, rebound tonometry wasmeasured at 8.82–9.2 mmHg (Keeney et al. 2019) (seeAppendix A). Ensure that fish are in a normal swimmingposition when collecting intraocular pressures to prevent anyartifactual changes from positioning.Similar to other vertebrates, fluorescein stain can be usedto document the presence of corneal ulcers, descemetoceles,or in extreme cases, corneal perforation. Serial use of fluores-cein stain can help to document the healing progress ofcorneal ulcers. It should be noted that cold-water speciesfish (those kept atdiagnosticworkup including radiographs/ocular ultrasound and bloodwork with culture is helpful to determine the cause of exoph-thalmos. Fine needle aspirates of retrobulbar space occupyinglesions can aid in ruling out abscesses, neoplasia, andgranulomas.Treating exophthalmia is dependent upon the etiology.Systemic antimicrobials and anti-inflammatories areindicated in many cases, common drug choices are providedin Box 5.2. In severe cases of exophthalmia or buphthalmos,enucleation may be indicated, particularly if it does notresolve with treatment, the protruding eye becomes severelydamaged, or the animal appears to have lost vision in theprotruding eye. Enucleation in fish is a relatively simpleprocedure and is discussed in greater detail by Sladky andClarke (2016). Under general anesthesia, the ring of cartilageand scleral tissue that holds the eye in the orbit are sharplyexcised with scissors. The optic vessels and optic nerve aresharply transected with scissors; hemorrhage tends to beminimal but in larger fish or fish with chronic inflammatorycondition the optic vessels may need to be ligated orcauterized. The authors use surgical absorbable gelatinsponges to pack the orbit after the globe is removed. Thereis insufficient adnexal tissue to close the orbit so the socket isleft open to heal by re-epithelialization (Fig. 5.15). Systemicantibiotics and anti-inflammatories should be administeredpost-operatively and the patient should be observed for anysigns of post-operative complications.Fig. 5.14 (a) Exophthalmia OD in a walleye surfperch Hyperprosopon argenteum due to supersaturation injury. (b) Chronic uveitis and lensluxation resulting in buphthalmos in a fantail goldfish Carassius auratus82 C. A. Parker-Graham et al.Buphthalmos is due to a prolonged increase in intraocularpressure, particularly in fish eyes due to their limited procliv-ity to stretch (compared to some mammalian eyes(Fig. 5.14b)). Idiopathic globe enlargement is seen as aninherited disease of certain species of goldfish, notably theblack moor goldfish (Matsumara et al. 1981). Globe size isincreased in these fish with enlargement of the vitreouschamber and subsequent myopia. This goldfish mutant hasbeen used as a model for studying the development of myo-pia associated with excessive scleral growth as occurs invisual deprivation myopia in species as widely separated asthe chicken and the tree shrew. Yew’s group in Hong-Konghas specifically investigated the metabolic events associatedwith the development of these large eyes (Lam et al. 2002),finding a marked elevation in lactic acid (Zhou et al. 2001)and presence of a previously unrecognized dicarboxylic6-member lactone ring carbohydrate, revealing a new metab-olite of glucose (Lam et al. 2002). Two peptides occur at highconcentrations in the vitreous humor in these eyes but thesignificance of these findings has yet to be fully investigated(Yew et al. 2001).Box 5.2 Common Drugs Used for OphthalmicPresentations in Fish PatientsAcetazolamide 6 mg/kg IM q24h.Amikacin 5 mg/kg IM q72h, 5 mg/kg ICe q24h � 3 days then 5 mg/kg ICe q48 h � 2 doses.Ceftazidime 22 mg/kg IM, ICe q72–96 h � 3–5doses.Danofloxacin 10 mg/kg IM q72h � 3–5 doses.Dexamethasone 1–2 mg IM, ICe.Enrofloxacin 10 mg/kg ICe q 96 h � 4 doses, 0.1%feed � 10–14 days.Florfenicol 10 mg/kg IM q24h (koi), 25–50 mg/kgPO q24h (koi).Meloxicam 1 mg/kg IM q24h.Source: Lewbart GA (2013) Fish. In: Carpenter JW(ed) Exotic animal formulary, 4th edn. Elsevier:St. Louis.EnophthalmiaEnophthalmia in fish has been associated with several viraldiseases such as koi herpesvirus or carp edema virus in koiCyprinus carpio. Enophthalmia may also be seen secondaryto emaciation as the fat pad behind the eye decreases in sizedue to inanition (Fig. 5.16).Fig. 5.15 Copper rockfish Sebastes caurinus three months post-enucleation. Note re-epithelialization and pigmentation of the ocularorbit following removal of the globeFig. 5.16 Enophthalmia associated with inanition and retrobulbar fatpad atrophy in a spawning coho salmon Oncorhynchus kisutch5 Ophthalmology of Osteichthyes: Bony Fish 83Gas Bubble DiseaseOcular gas bubble disease occurs when gas accumulates inthe retrobulbar, adnexal, or intraocular tissues and causesdamage due to occupation of space. Gas bubble disease ismost commonly reported in the literature as being caused bysupersaturation disease or barotrauma in fish patients. How-ever, in one author’s experience (Stevens), it has also beenseen in cases of observed trauma without any previous his-tory of gas supersaturation events or barotrauma and traumaaccounts for the majority of gas bubble disease cases that arepresented in a public aquarium facility (Fig. 5.17a).Ophthalmic manifestations of gas bubble disease includeexophthalmia (unilateral or bilateral), intrastromal cornealgas bubbles, gas bubbles in the anterior chamber, periorbitalemphysema, anterior synechiae, cataracts, iridal hemorrhage,and panophthalmitis (Smiley et al. 2012). Histologically gasemboli can usually be appreciated in the choroid gland, asthis is where oxygen concentrates in the eye (Speare 1990).Changes induced in multiple ocular structures can lead toblindness through compression and degeneration of tissuessurrounding emboli, retinal detachment, and optic nervestretching. Corneal rupture and avulsion of ocular contentscan occur in severe cases. Outbreaks of gas bubble diseasehave been noted in a number of species of farmed fish (Saeedand Al-Thobaiti 1997) and also in some wild fish, bothfreshwater and marine. In larvae bubbles are most obviousin the subcuticular tissue, but in adult fish bubbles areobserved in the eye, skin, gills, and mouth as well as theswim bladder and peritoneum at post-mortem examination.Other causes of ocular choroidal gland enlargement include acondition in which excess carbonic anhydrase in the choroi-dal gland causes malfunction. Intraperitoneal gland injectionsof carbonic anhydrase inhibitors can ameliorate the signs(Dehadrai 1966; Bouck 1980). Other conditions can mimicgas bubble disease by causing exophthalmos, includinggenetic pseudoalbinotic ophthalmia in Atlantic salmon Salmosalar to mycobacterial granulomatosis in freshwater fish.Supersaturation injury can occur when the total pressureof dissolved gases (usually nitrogen or oxygen) in waterexceeds atmospheric pressure; gases come out of solution incirculation and form gas emboli in the body, most commonlyin gills, fins, skin, and eyes. Acute supersaturation events willoften result in acute, sometimes mass mortality, with fry andsmolts exhibiting behavioral abnormalities prior to lethargyand loss of balance. Necropsy findings can include swimbladder overextension with abdominal distention, gas cov-ered skin swellings, gas bubbles clearly visible in the yolksac, gills, and fin rays as well as exophthalmia. Chronic gasbubble disease occurs with low supersaturation levels fromfaulty pipework sucking air into a moving body of water orfrom water falling over s slipway. In such cases mortality islow (oroverproduction of oxygen due to photosynthesis in a plantedsystem.Fig. 5.17 Gas bubble disease in fish. (a) Exophthalmia in a semicircleangelfish Pomacanthus semicirculatus secondary to trauma. (b) Exam-ple of a hyperbaric chamber at a public aquarium used to treat fishsuffering from barotrauma or gas supersaturation disease. (c) Fineneedle aspiration of retrobulbar gas from an anesthetized canary rockfishSebastes pinniger. (c—Photo courtesy of Jamie Gerlach)84 C. A. Parker-Graham et al.Barotrauma is the physical damage caused by decreasingpressure when fish are brought rapidly from depth to thewater’s surface as is commonly performed by anglers orthose collecting specimens at depth for scientific study. Phys-ical damage is caused in physoclistous species (those specieswithout a connection from the swim bladder to the esopha-gus) as the gas in the swim bladder rapidly distends due todecreasing pressure as depth is decreased. Exophthalmia andocular emphysema are among some of the most commonclinical signs that are encountered in fish that have experi-enced barotrauma. The mechanism is thought to be caused bygas leaking from the swim bladder and tracking along thefascial planes of the cranium to the retrobulbar space andperiocular tissues (Hannah et al. 2008).Regardless of its cause, treatment of gas bubble disease isaimed at eliminating the presence of gas bubbles orpreventing their further accumulation and providing support-ive care. In cases of supersaturation, identifying andcorrecting the cause of supersaturated water is paramount.Because of the systemic stress of a supersaturation eventsupportive care, such as salting a freshwater system andmonitoring for viral and bacterial outbreaks, is important.An unusual cause of exophthalmos and intraocular gas bub-ble and cyst formation has been documented in farmedAtlantic halibut Hippoglossus hippoglossus (Williams et al.1995). These fish usually live at considerable depth andfarming them in shallow tanks led to the oxygen producedby their choroidal glands coming out of solution especiallywhen they became aggressive during feeding (Williams et al.1998) leading to cyst formation and blindness (Williams andBrancker 2018). An increase in their choroidal gland car-bonic anhydrase levels was also associated with the condition(Williams and Brancker 2006) but the solution was a simpleone—feeding the fish so as to separate them rather thanconcentrate them in one area of the tank reduced aggressionand eliminated the problem.If ocular gas bubbles can be seen or are detected viaradiography or ultrasonography, increasing the amount ofbarometric pressure can be of great therapeutic benefit. Thiscan be achieved either through forced submersion back todepth (commonly performed by anglers with a variety ofdevices) or by providing hyperbaric therapy via a pressurechamber. Several public aquariums now own and operatehyperbaric chambers to treat cases of barotrauma or gasbubble disease in a clinical capacity as well as during fishcollection trips. Figure 5.17b illustrates one such hyperbaricchamber. For treatment of gas bubble disease, the fish isplaced within the chamber and then the pressure is slowlyincreased until the exophthalmia resolves or lessens, theocular bubbles disappear/are reduced in size or until aneffective therapeutic pressure is reached. At the author’sfacility, a therapeutic pressure of ~30 PSI (equivalent todepth of ~65 ft) is used for tropical species whereas atherapeutic pressure of ~40 PSI (equivalent to ~90 ft) isused for cold-water species. For tropical species, generally~12–24 h maintained at therapeutic pressure is sufficient tohelp resolve gas bubble disease whereas for cold-water spe-cies oftentimes 3–5 days may be required. At the end of thetreatment period, the pressure in the chamber is loweredslowly (~2–3 PSI/30 min-2 h for tropical species vs 1–2PSI/hr-2 h for cold-water species) back to ambient pressurewhile monitoring and adjusting for signs of excessivebuoyancy.Other treatment options for visible ocular bubbles or airpockets noted on radiography or ultrasonography include fineneedle aspiration with or without ultrasound guidance(Fig. 5.17c). It should be noted however that this methodcan have serious consequences such as introduction of infec-tion or a significant bleeding resulting in hyphemia or a blotclot in the retrobulbar space or choroid which is very slow toresolve. For this reason hyperbaric therapy is preferred overaspiration if possible.Carbonic anhydrase inhibitors, like acetazolamide, havebeen used with varying success for resolution of gas emboliin affected fish (Box 5.2). Supportive care with antibiotics toprevent secondary bacterial infection and anti-inflammatoriesto help control pain and inflammation are also generallywarranted. Another technique that has been described forchronic cases that are refractory to treatment and environ-mental correction is pseudobranch ablation in which thepseudobranch is rendered non-functional with cautery in anattempt to prevent oxygen from being concentrated in thechoroidal gland inappropriately.Corneal DiseaseThe corneal surface is in constant contact with the fish’senvironment, making it particularly susceptible to physicaland chemical injury. Keratitis from damage to the cornea iscommon in fish (Wilcock and Dukes 1989), both fromtrauma and inappropriate water quality. Corneal damage inaquaculture often occurs in transportation or overcrowding(Brandt et al. 1986; Nicol 1981), while long-term environ-mental and nutritional influences are important innon-traumatic lesions.Non-ulcerative keratitis presents as diffuse, opaque gray-blue haze on the corneal surface, corneal edema, andneovascularization (Fig. 5.18a). In severe or chronic casesbullae may form and cause corneal erosion and granulation.The most common causes of keratitis are excessive ultravio-let light exposure, nutritional deficiencies (riboflavin,vitamin A, thiamine), and poor water quality. Opacificationand keratitis have been affiliated with Vibrio harveyiinfections in some species (Williams 2012). On examinationcellular infiltrates may be noted in the cornea. Additionally,fish develop corneal edema more quickly and to a greaterdegree than terrestrial animals, thus corneal edema is a5 Ophthalmology of Osteichthyes: Bony Fish 85common clinical sign of general corneal disease (Fig. 5.18b).Non-ulcerative keratitis will not take up fluorescein stainimmediately, but after a few minutes you may notice granularstain uptake, which indicates that the tight junctions in thecorneal epithelium are damaged. Bacterial and fungal coloni-zation of damaged cornea can cause panophthalmitis andbuphthalmos or phthisis bulbi, even if non-ulcerative(Fig. 5.18a). Ocular involvement in lymphocystis infectioncan manifest as corneal, conjunctival, iridal, or choroidalnodules (Russell 1974). Phototoxic corneal damage hasbeen reported in salmonids (Hoffert and Fromm 1965;Edelhauser et al. 1969) while deficiency of thiamine,vitamin A, and riboflavin causes corneal lesions as well asintraocular pathology leading to corneo-lenticular fusion insevere disease (Hughes et al. 1981). Corneal lipidosis hasbeen documented in several species of eels in public aquariaand has been noted clinically in a few other species(Fig. 5.18c). Ocular lipid deposition may be related to captivediets and lifestyle; documented cases have been noted to havehigher plasma protein, higher cholesterol, and highertriglycerides than wild-caught counterparts. Clode et al.found that surgical lipid keratectomy and dietary manage-ment (low-fat) were viable means of managing this disease incaptive eels (Clode et al. 2012).Treating non-ulcerative keratitis is difficult and oftenremains unresolved in the first fish that are affected. Thegoal of treatment is to identify possible shortcomings in theenvironment, nutrition, and waterquality to prevent keratitisdevelopment in more of the population. In severe cases withextensive damage, suspected discomfort, or secondarycomplications such as protracted uveitis or recurrent ulcera-tion, enucleation may be considered to reduce discomfort, therisk of globe perforation, and secondary infection.The confluence of the skin with the cornea increases theprobability that keratitis can occur via skin parasites (e.g.,monogenetic trematodes, digenetic metacercariae,turbellarians, myxosporidia), water pollution, and viralinfections (Jurk 2002; Williams 2019; Boonthai et al.2018). Parasitism with the monogenetic trematodeNeobenedenia melleni is common in coastal cold-water tele-ost species. When viewed in seawater, these monogeneansare translucent and can be difficult to visually appreciate(Fig. 5.19a,b). Chronic attachment of monogeneans to thecornea can cause corneal ulceration and edema, and removalof the parasitic infection can also cause ulceration(Fig. 5.19c). Treatment options for monogeneans includefreshwater dips (placing marine fish in a pH andtemperature-matched freshwater bath for 3 to 5 minutes) orpraziquantel baths (1 to 3 h). When placed in freshwatermonogeneans become opaque due to osmotic shock andcan easily be appreciated (Fig. 5.19b). In one author’s facility(Stevens), fish that are too large for traditional praziquantelbaths are trained to accept underwater topical application ofhighly concentrated praziquantel solution (10 g/L)administered via syringe. Application of praziquantel bythis method stuns monogeneans and they either releasefrom the cornea or can be manually removed by divers.Other parasitic species, such as Ichthyobodo,Ichthyophthirius, Glugea, Cryptocaryon, Tetrahymena,Henneguya, and digenetic trematode metacercariae, amongothers, can extend from the skin onto the surface of thecornea (Hoffman 1999) (Fig. 5.20).Digenetic trematode metacercariae can be involved inanterior and posterior ocular disease and are importantenough that we will discuss them in greater detail below.Some copepods can burrow into the cornea and, if theypenetrate the globe can give a granulomatous response inthe anterior segment. Corneal damage resulting ingeneralized ocular damage has been reported to be moreprevalent when fish are held at their upper temperature limitsFig. 5.18 Non-ulcerative keratitis in fish. (a) Severe corneal edema,hyphema, and corneal neovascularization in a cultured rose snapperLutjanus guttatus diagnosed with a systemic infection of Streptococcusiniae. (b) A scorpionfish species photographed in its natural habitat withcorneal edema of the right eye. (c) Corneal lipidosis in a Californiamoray eel Gymnothorax mordax. (b—Courtesy of David G.Heidemann)86 C. A. Parker-Graham et al.(Lee et al. 1976). Additionally, non-parasitic or mutualisticspecies can be found on the eyes of fish and should not beremoved or disturbed. For example, Bruun’s cleaning partnershrimp Urocaridella antonbruunii cleans the cornea andperiocular skin of dead cells, other debris, and parasites(Fig. 5.21).The definitive diagnosis of corneal ulceration is made bydemonstrating fluorescein stain uptake in the affected region.Hypothetically, tricaine can interfere with stain uptake byskin and corneal ulcers by quenching fluorescence of thestain, resulting in a false negative. Therefore, the cornealsurface should be rinsed with dechlorinated, anesthetic-freewater prior to staining (Davis et al. 2008), although this hasnot become evident in the authors’ experience. Culture datafrom a corneal ulcer typically represent the bacterial milieu ofthe water column and is not typically of clinical value. Cytol-ogy, on the other hand, can be important particularly if fungalinfection is suspected. Samples can be gently collected by acytology brush and allowed to air dry on a slide beforestaining.In fish, even superficial corneal ulcers should be addressedrapidly and aggressively. The stroma is at risk of infectionand colonization from water-borne pathogens (notably fungiand gram-negative bacteria) and compromise of the cornealepithelium represents a risk of osmoregulatory imbalance forthe fish that can cause marked corneal edema (Fig. 5.22).Corneal ulceration can progress rapidly to globe rupture.Regular topical treatment of corneal ulcers in fish is notpractical because of their aquatic lifestyle, however topicalantimicrobial ointment can be applied to a corneal ulcer whilethe fish is anesthetized for examination. The topical medica-tion should be allowed to absorb for at least one minutebefore placing the fish back in water. Systemic antimicrobialsare more commonly used. A table of drugs commonly usedfor fish is supplied in Box 5.2. Any antimicrobial choiceshould address gram-negative bacteria, as these are the mostcommon environmental pathogens in the aqueous environ-ment. The fish’s aqueous environment may be used to advan-tage by treating with immersion compounds. Broad-spectrumantimicrobials, such as nitrofuran, have been used for treat-ment of secondary infection of corneal ulcers (Williams2012); however, rules governing the use of antimicrobialsin fish should be considered as they change from country tocountry. For examples, in some locations all fish species areconsidered food and thus nitrofuran use is illegal. For fresh-water species, salting the system to a target of 3 to 5 g/L willhelp mitigate osmotic losses through the damaged cornea.Ozone or ultraviolet sterilization of the fish’s system watermay be considered for systems with chronic ulceration issues.Progressing stromal corneal ulcers should warrant consid-eration of additional intervention to prevent advancement to adescemetocele and/or globe rupture. Cyanoacrylate glue canbe used for tectonic support. The eye of the anesthetizedpatient should be held out of the water for glue application.A small bead of antimicrobial ointment or a drop of antimi-crobial solution can be applied prior to the glue and allowedto absorb for at least one minute. The ulcer bed should begently dried with a cotton-tipped applicator or Weck-Celsponge as glue will not adhere well to a wet surface. Asmall drop of cyanoacrylate glue is then applied to the ulcerbed and allowed to dry before returning the fish to water.Appropriately applied, a cyanoacrylate patch will last for fiveto ten days. This method should not be used if adescemetocele is suspected, as the exothermic reaction ofdrying cyanoacrylate can rupture the globe in this situation(Jurk 2002).LensThe teleost lens is typically a spherical crystalline structurethat enlarges as the fish grows and plays the sole role of lightFig. 5.19 Monogenetic trematodes of fish keratitis. (a) Monogenetictrematode Neobenedenia melleni attached to the corneal surface of agiant seabass Stereolepis gigas. Note the translucence of the parasite inseawater. (b) Monogenetic trematode N. melleni attached to the cornealsurface of a black rockfish Sebastes melanops in a freshwater bath. Noteopacification of the parasite due to osmotic shock, which facilitatesvisualization. (c) Fluorescein stain uptake on the cornea of a copperrockfish Sebastes caurinus immediately after removal of monogeneanparasites from the corneal epithelium5 Ophthalmology of Osteichthyes: Bony Fish 87refraction in the fish’s eye. In some species, it serves addi-tional functions such as acting as light filters (Somiya 1982)and in globe degeneration (Yamamoto and Jeffery 2000).During development, the lens forms from surface ectodermthat delaminates into the eye as a solid cell cluster. Aroundthe lens nucleus, lens fibers proliferate in a circular fashion toform concentric shells (Dahm et al. 2007). On the outersurface of the lens, fibers converge in one of three forms:(1) umbilical or “point” sutures (e.g., zebrafish, Greiling andClark 2012), “Y”-shaped sutures (Bantseev et al. 2004), orthe common line suturesandGharials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299Paoul S. Martinez and Caryn E. PlummerPart IV Aves16 Introduction to Ophthalmology of Aves . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321Bret A. Moore, Esteban Fernandez-Juricic, Michelle G. Hawkins, FabianoMontiani-Ferreira, and Rogério Ribas Lange17 Ophthalmology of Psittaciformes: Parrots and Relatives . . . . . . . . . . . . . . . 349Bret A. Moore, Arianne Pontes Oriá, and Fabiano Montiani-Ferreira18 Ophthalmology of Passeriformes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393Bret A. Moore, Esteban Fernandez-Juricic, and Fabiano Montiani-Ferreira19 Ophthalmology of Coraciimorphae: Toucans, Hornbills, Woodpeckers,Kingfishers, and Relatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415Erin M. Scott and Sharman Hoppes20 Ophthalmology of Accipitrimorphae, Strigidae, and Falconidae: Hawks,Eagles, Vultures, Owls, Falcons, and Relatives . . . . . . . . . . . . . . . . . . . . . . . 429Bret A. Moore and Fabiano Montiani-Ferreira21 Ophthalmology of Gruiformes and Aequorlitonithes: Flighted Seabirds &Relatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505Mikel Sabater González22 Ophthalmology of Sphenisciformes: Penguins . . . . . . . . . . . . . . . . . . . . . . . 537Melanie Landry Church23 Ophthalmology of Strisores: Nightjars, Frogmouths, Swifts, Hummingbirds,and Relatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551Bret A. Moore, Fabiano Montiani-Ferreira, and Antonia Gardner24 Ophthalmology of Galloanserae: Fowl, Waterfowl, & Relatives . . . . . . . . . . 571H. L. Shivaprasad, Fabiano Montiani-Ferreira, and Bret A. Moore25 Ophthalmology of Palaeognathae: Ostriches, Rheas, Emu, Cassowaries,Tinamous, and Kiwis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 627Maria Luisa Pérez Orrico and Mikel Sabater GonzálezAppendix A: Normative Ocular Data (Clinical Tests and MorphologicalParameters) in Wild and Exotic Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649Appendix B: Pharmacological Mydriasis in Birds . . . . . . . . . . . . . . . . . . . . . . . . 665References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675xiv ContentsAbout the EditorsFabiano Montiani-Ferreira is currently a Full Professor of Com-parative Ophthalmology at the Federal University of Paraná, Brazil(UFPR), where he teaches veterinary and graduate students andtrains veterinary ophthalmology residents, since 1997. Hecompleted the Senior Veterinary Student Program at the AnimalMedical Center, New York, USA. He then obtained his Bachelor ofVeterinary Medicine (BVetMed) and a Master of Science (MSc)degree in Veterinary Sciences from the same university (UFPR). Inthe early 2000s, he obtained a Doctor of Philosophy (PhD) degreefrom Michigan State University (MSU). Dr. Montiani-Ferreiracurrently holds an official position and grant as a certified veteri-nary researcher (PQ2) at the Brazilian National Council for Scien-tific and Technological Development (CNPQ) and is a Diplomateof the Brazilian College of Veterinary Ophthalmologists(DBCVO). His research activities focus on (1) ocular morphology,physiology, clinical tests, and vision in wild and exotic animals;(2) investigations on animals carrying spontaneous mutations insmall animals as models for the study of inherited retinal diseasesin humans; and (3) nature and practice of science in addition tomedical biostatistics. His clinical interests include (1) inheritedretinal diseases in domestic and non-domestic animals; (2) adaptingestablished ophthalmic procedures for wild and exotic animals;(3) and general ophthalmic surgery.Bret A. Moore is currently an Assistant Professor of ComparativeOphthalmology at the University of Florida. He holds a Bachelor ofScience in Neurobiology and Physiology (BS), Doctor of Veteri-nary Medicine (DVM), and Doctor of Philosophy (PhD) fromPurdue University, and completed his postdoctoral training/resi-dency in comparative veterinary ophthalmology at the Universityof California, Davis. His research occupies a unique niche thatcombines vision, visual ecology, and clinical ophthalmology.From an ecological perspective, his research asks questions thatexplore unknown or unexplained morphological and physiologicaladaptations in vision, and seeks to understand the role of multiplevisual parameters simultaneously in order to better understand agiven species’ “visual space,” importantly how visual systemsalign with behavior and enable success in respective ecologicalniches. Clinically, his research interests are focused on understand-xixing disease processes as well as diagnostic and surgical methodol-ogy in exotic animal species. By taking this multifaceted approachto vision and clinical ophthalmology, and evaluating theirinteractions together, questions can be answered that not onlybridge the gap across disciplines, but also become translatable toother disciplines such as conservation biology and the developmentof new biotechnologies.Gil Ben-Shlomo (1970–2020) held DVM and PhD degrees fromthe Hebrew University of Jerusalem, Israel. Following a compara-tive ophthalmology residency at the University of Florida, heobtained board certification and Diplomate status in the Americanand European Colleges of Veterinary Ophthalmologists. His latestservice was as faculty at the College of Veterinary Medicine,Cornell University, where he taught veterinary and graduatestudents and trained residents in the field of veterinary ophthalmol-ogy. He had been invited to speak at numerous local, national, andinternational conferences. Prof. Ben-Shlomo was also an associateeditor and author of Gelatt’s Veterinary Ophthalmology (sixthedition), was an editorial board member of the journal VeterinaryOphthalmology, and was the most recent President of the Interna-tional Society of Veterinary Ophthalmology.xx About the EditorsPart IEarly Photoreception, Invertebrates, and FishesEvolution of Photoreception and the Eye 1David L. WilliamsIntroductionAround 580 million years ago the first animals with bilateralsymmetry are seen in the fossil record in the so-called Cam-brian explosion. This rapid development of complexlifeforms seems very much integrated with the developmentof vision, with well-developed optics seen in some of theearliest arthropods from simple ocelli (Schoenemann andClarkson 2012) to highly developed compound eyes oftrilobites (Clarkson et al. 2006) with complex optics, (Leeet al. 2011) and compound eyes similar to those seen in theinsects of today (Paterson et al. 2011; Zhao et al. 2013). Priorto expanding to our most clinically relevant species, thevertebrates, it will be worthwhile to track ocular evolutionfrom protozoa through the earliest eyespots of flatworms, toprovide perspective as we build toward the camera-like eyewe know in dogs, cats, horses, and humans today. Followinga discussion of evolution of the early eye and photoreception,the eyes of invertebrates will be discovered. Finally, we willsee that the earliest fish play a fascinating part in this evolu-tionary tale.The Evolution of the EyeDarwin is regularly quoted as recognizing the developmentof the eye as a significant difficulty for his theory of evolutionby natural selection. He writes in The Origin of Species(Darwin 1859):To suppose that the eye, with all its inimitable contrivances . . . .could have been formed by natural selection, seems, I freelyconfess, absurd in the highest possible degree.(Bantseev et al. 2004).Lenticular disorders, particularly cataracts, are a commonpresentation in many species of fish. Cataracts are infre-quently appreciated in the immature stage and usually presentas mature or complete lesions, both in captive (Fig. 5.23a) orfree-living individuals (Fig. 5.23b). Histologically, fishFig. 5.20 Examples of unknown trematode worms (red arrows) causing keratitis in balloonfish Diodon holocanthus of the Southern coast ofFlorida, USA. (Courtesy of David G. Heidemann)88 C. A. Parker-Graham et al.cataracts appear very similar to mammalian or avian cataractsand are associated with hydrophobic swelling of the lens,lysis of lens fibers, epithelial hyperplasia, and intralenticularmigration of surface epithelium (Jurk 2002). Cataracts can begraded systematically on a scale of 0–3, which takes intoaccount the symmetry of the cataracts, transparency of thelens and whether changes are present only in the anterior oralso in the posterior cortex (Bjerkås et al. 1996). Severityprogresses from a score of 0 in a fish with healthy eyes, to ascore of 3 that show bilateral cataracts with anterior andposterior cortical changes. Chronic cataracts can ruptureand extrude nuclear material into the eye, causing uveitis orpanophthalmitis (Bjerkås et al. 1998). Uveitis provoked bycapsular rupture and resorption of the cataract has beendescribed, with retinal detachment related to vitreal degener-ation (Shariff et al. 1980).The etiologies of cataracts are wide and varied, includingexcessive ultraviolet light exposure, nutritional deficiencies(methionine, zinc, riboflavin, vitamin A, vitamin C),nutritional excesses (minerals), rapid fluctuations in watertemperature and salinity, poor water quality,panophthalmitis, intralenticular migration of parasites(Diplostomum spp. metacercariae), toxin exposure, andgenetic predisposition (Williams 2012; Jurk 2002; Ravneetand Sharma 2009). Lens changes in systemic granulomatosishave been described in gilthead bream Sparus aurata fedunsuitable fishmeal diets (Paperna et al. 1980). One com-monly seen cause of cataracts in fish is parasitism as notedabove. Specifically, the trematode Diplostomum spathaceumis a cause of cataract formation in many fish living in fresh-water and brackish water habitats as noted above (Fig. 5.24).For individuals that have developed cataracts,Fig. 5.21 Parasitic or mutualistic species in fish that should not bemistaken for causing keratitis. (a) An unknown fish species with acopepod parasite attached to skin ventronasal to the left eye. Somecopepods can cause ocular injury if they attach to the corneal surface.(b–e) A great example of mutualism, the Bruun’s cleaning partnershrimp Urocaridella antonbruunii cleaning the eyes of dead skin anddebris of a (b) Pufferfish species, (c) an unknown eel species, (d) anUndulate moray eel Gymnothorax undulates, and (e) a Moray eelspecies. (a—Used with permission from Shane Gross, Shutterstock.com. b—Used with permission from Thomas Pommerin, Shutterstock.com. c—Courtesy of David G. Heidemann. d—Used with permissionfrom Shahar Shabtai, Shutterstock.com. e—Used with permission fromRich Carey, Shutterstock.com)5 Ophthalmology of Osteichthyes: Bony Fish 89http://shutterstock.comhttp://shutterstock.comhttp://shutterstock.comhttp://shutterstock.comhttp://shutterstock.comhttp://shutterstock.comphacoemulsification and aspiration of the lens have beenperformed successfully in the cartilaginous fish Gulfsturgeons Acipenser oxyrinchus desotoi, but have not yetbeen reported in teleost species (Bakal et al. 2005). Somesources however suggest that because fish lenses areextremely hard compared to mammalian lenses due to highprotein and water content, surgical removal of cataractsshould not be attempted (Whitaker 2001; Kozłowski andFig. 5.22 Left corneal laceration and pronounced stromal edema due to environmental water influx in a striped burrfish Chilomycterus schoepfi.(Courtesy of David G. Heidemann)90 C. A. Parker-Graham et al.Kröger 2019). Medical treatment of diplostomiasis is morecommon and involves the use of praziquantel either by sub-mersion in medicated water baths, medicated dips or feedmedication (Plumb and Rogers 1990; Szekely and Molnar1991; Bader et al. 2019).Dietary factors play a major role in cataract formation incaptive fish populations and these include deficiencies orimbalances in vitamins, amino acids, and minerals. Ribofla-vin (vitamin B2) deficiency induces epithelial thickening andopacity in the cornea and lens opacity originating in theposterior cortex (Hughes et al. 1981). Vitamin A is alsoimportant in preventing cataract formation and astaxanthinin salmon diets act as provitamin A (Torrissen andChristiansen 1995). Deficiencies in methionine which usedto be common in salmonid fish fed soy-based products defi-cient in this amino acid resulted in degeneration andopacification of the lens starting from the lens capsule andprogressing toward the nucleus (Poston et al. 1977). Simi-larly, dietary histidine and tryptophan deficiencies can alsolead to cataract formation, which is often seen in farmed fish(Walton et al. 1984; Peachey et al. 2018). Specifically, afterthe debacle of bovine spongiform encephalopathy caused bythe feeding of bone meal (rendered slaughterhouse wasteproducts) to cattle, feeding of this to any animal was banned.This led to dietary deficiencies, specifically in histidine,which caused cataracts in farmed fish (Breck et al. 2003;Waagbø et al. 2010; Wall 1998). In Atlantic salmon Salmosalar smolts, high tissue vitamin C and astaxanthin statuscorrelated with decreased frequency of cataract development,while high body levels of lipid, Mn, and Fe are related tocataract formation likely by promoting oxidative stress(Waagbø et al. 2003). Another mineral that plays a majorrole in cataract prevention is Zn, which is best absorbed in theforms of ZnNO3 or ZnSO4 (Satoh et al. 1987). Correct Znsupplementation is found to reduce incidences of cataract,however high level of tricalcium phosphate (hydroxyapatite)often found in white fish meal-based diets results in reducedZn bioavailability and the need for increased supplementa-tion (Satoh et al. 1997).Ultraviolet radiation (UV) has been implicated as anothercause of cataracts in teleost fish via the direct effect ofinducing lens fiber swelling and anterior sub-capsular epithe-lial cell damage (Cullen and Monteith-McMaster 1993).However, unlike UV-induced cataracts in mammals, directUV damage is not the only way by which UV can inducecataract formation. The combination of UV and environmen-tal factors can indirectly create cataracts in fish by causingoxidative stress. Dissolved organic matter helps attenuate UVpenetration in the water, but its exposure to UV can also leadto the catalysis of redox reactions that produce reactive oxy-gen species such as hydrogen peroxide and oxygen freeradicals. Furthermore, the presence of pollutants such aspolycyclic aromatic hydrocarbons can be photoactivatedand result in the further production of reactive oxygen species(Zagarese and Williamson 2001). In fact, UV-treated waterhas been found to increase the incidence of cataract formationin juvenile cod Gadus morhua (Björnsson 2004). Interest-ingly, UV filters are often used in non-commercial settings toreduce pathogen load for pet fish, but UV is rarely blamed asthe culprit for cataract formation in pet fish, suggesting thatFig. 5.23 Cataracts in fish. (a) A complete cataract in a copper rockfishSebastes caurinus. (b) A complete cataract and corneal edema, likelysecondary to either uveitis with possible lens capsule rupture, in a free-living scrawled filefish Aluterus scriptus. (a—Courtesy of JamieGerlach. b—Courtesy of David G. Heidemann)5 Ophthalmology of Osteichthyes: Bony Fish 91cataracts in pet fish exposed to UV-treated water may beeither underreported or that the higher qualitywater givento pet fish may result in low incidences of UV-inducedcataracts.Osmotic challenge to the eye can lead to cataract forma-tion in teleost fish. Sudden exposure to environments of lowsalinity is one of the most common reasons for cataracts incaptive fish. These cataracts are usually bilateral and areresultant from water infiltrating into the lens, causing thelens to no longer let light through (Bjerkås et al. 1998).Osmotic cataracts can have a characteristic appearance thatcan be identified on ophthalmological exam of the live fish.These lenses are primarily hazy in the anteriorly, with visiblewidening of the lens sutures. Some cases develop vacuoles orproteinaceous lakes in the lens cortex, which can also be seenwith the naked eye. The lens may be swollen such that it takesup the entire pupil and covers the aphakic space. In farmedteleost species, osmotic cataracts are often related to hus-bandry, especially in anadromous species such as Atlanticsalmon, when young stock that have not completedsmoltification are placed into sea pens. However, as long asparr are moved into seawater during the “smolt window,”osmotic cataracts would resolve within 1–2 weeks as gillNa+-K+-ATPase activity adjusts for the hypoosmoregulatorycapacity increases (Bjerkås et al. 2003). Natural fluctuationsin salinity levels can also lead to multiple occurrences andFig. 5.24 TrematodeDiplostomum spathaceuminfection in the lens of anunknown fish species. (Courtesyof the Comparative OcularPathology Laboratory ofWisconsin)92 C. A. Parker-Graham et al.resolution of osmotic cataracts in farmed fish. Such repeatedosmotic challenges to the lens may predispose the lens todeveloping irreversible cataracts, which if occurred in thejuvenile fish, can result in perinuclear cataracts in the adultfish where healthy lenticular tissue is laid down around anearlier cataract during the fish’s growth (Breck andSveier 2001).With the intensive breeding for faster growth in farmedfish, increased growth rates have been found to be linked withcataract formation. A genetic factor for cataract predisposi-tion has been found in multiple species including tilapiaOreochromis mossambicus (Noga et al. 1981), Atlanticsalmon (Bjerkås et al. 1996), and lake trout Salvelinusnamaycush (Kincaid and Elrod 1991). In Atlantic salmon,triploidy has been linked to a greater likelihood of cataractdevelopment during growth (Wall and Richards 1992),although the loss of vision due to cataracts may not be thesole cause for reduced growth (Taylor et al. 2013). Thereason for this predisposition in triploid salmon goes backto nutrition as they have a higher requirement for dietaryhistidine, which can lead to triploid salmon with severecataracts being smaller than their diploid counterparts atharvest due to an inability to feed effectively (Taylor et al.2015). Rapid growth in fish artificially selected for this traitmay also predispose the lens to a lack of essential nutrients orout capacitate enzymatic systems in the lens, leading to thedevelopment of cataracts (Ersdal et al. 2001).Increased water temperature is another factor in cataractformation in fish. Atlantic salmon parr that are exposed toconstantly high temperatures or fluctuating temperaturesexperience the fastest growth rate but also more severecataracts, which continue to worsen after transfer to the sea(Bjerkås et al. 2001). There are many suggested pathophysi-ological mechanisms suggested for temperature-relatedcataracts in fish, including high temperatures promotingdiplostomiasis (Karvonen et al. 2013), high temperatureshindering the hexose monophosphate shunt’s capacity forenzymatic glucose metabolism leading to diabetes-likecataracts as excess glucose is metabolized into sorbitol(Hoffert and Fromm 1970), or inappropriate temperaturesaffecting the ability of lens α crystallins to protect γcrystallins from heat denaturation (Kiss et al. 2004). Theimpact of changing water temperatures has mostly beenstudied in farmed fish populations, but rising temperaturescaused by global warming may undoubtedly have an impacton the lenses of wild species.In addition to temperature factors within the environment,chemical pollution can induce cataract formation in fish.Habitat contamination with polycyclic aromatichydrocarbons (PAH) is often cited as the reason for cataractsfound in wild fish populations. Moreover, PAH exposure alsoproduces other co-morbidities including skin ulceration, finrot, tumors, and lesions in other parts of the eye (Hargis andZwerner 1988). Combined in vitro exposure of trout lenses toPAHs (fluorene, fluoranthene and benzopyrene) and UVirradiation has been shown to result in cataractogenesis dueto the photoactivation of PAHs (Laycock et al. 2000). Sele-nium is another pollutant that can lead to long lasting mor-bidity and mortality in fish. Cataract formation along withedema causing exophthalmos are more recognizable signs ofselenium toxicity, however recirculation of this pollutant in ahabitat can last for decades in a habitat and present moreinsidious signs such as reproduction failure (Lemly 2002).Clinically, the presentation of an opaque lens may beassociated with a recent onset of inappetence, loss of condi-tion, bumping into tank furnishings, increased aggression bytank mates, or recent changes in skin color. Some cases ofcataracts can be reversed, depending upon the etiology, ifdetected early and immediate steps are taken to correct anyenvironmental or nutritional issues. In those cases that do notresolve and reduced vision is detrimental to the animal’squality of life removal of the lens may be considered. Thedensity of the fish lens, shape of the pupil, and generallysmall size of the eye make phacoemulsification difficult,although there are at least two reports in the literature ofphacoemulsification being successful (Williams 2012;Bakal et al. 2005). More commonly an intracapsular orextracapsular lensectomy is performed. The authors preferan intracapsular approach if possible to reduce the risk ofsecondary inflammation and panophthalmitis.There is at least one published report of anterior lensluxation in a fish patient (DeSilva et al. 2010). The authorshave seen several cases of anterior and posterior lens luxationsecondary to severe gas bubble disease and secondary totrauma (Fig. 5.14b). As in other species, anterior lens luxa-tion can cause glaucoma and lensectomy or enucleation maybe considered in these cases.UveitisUveitis is typically secondary to an underlying systemicinflammatory disease process (Fig. 5.25); septicemia due togram-negative bacterial infection (commonly Aeromonasspp. or Pseudomonas spp.), helminth migration, Myxobolusspp. infection, trauma, and post-vaccinal reaction have allbeen implicated in the development of uveitis in fish(Williams 2012; Koppang et al. 2004). Intraocular diseasecan also cause uveitis, such as uveal neoplasms, advancedcataracts, and lens luxation. Uveitis is definitively diagnosedby observing cellular infiltrates in the anterior chamber,hyphema, or hypopyon. Cases of uveitis also commonlypresent with episcleral hyperemia, corneal edema, aqueousflare, posterior synechiae, exophthalmia, retinal detachment,lethargy, and inappetence. Because of the small size of thefish eye and close proximity of ocular structures to one5 Ophthalmology of Osteichthyes: Bony Fish 93another, uveitis often presents as panophthalmitis (Jurk2002). In chronic cases the globe can develop glaucomaand buphthalmos, and eventually becomes phthisical andnon-visual. A diagnosis of uveitis or panophthalmitiswarrants a more extensive diagnostic workup to identify theunderlying cause. Because of the severity of bacterialinfections antimicrobials are often started while waiting forculture blood results, and selected antimicrobials should havea good spectrum of activity against gram-negative bacteria.Systemic anti-inflammatoriesare indicated.NeoplasiaThe study of neoplasia in fish is rapidly expanding andtumors have been documented associated with almost everyorgan system in fish (Vergneau-Grosset et al. 2017). Whilenot commonly diagnosed, ocular neoplasms can arise fromany part of the eye (Fig. 5.26). Clinical signs associated withocular neoplasms are varied and nonspecific, such asbuphthalmos, exophthalmos, glaucoma, uveitis,panophthalmitis, apparent blindness, lethargy, inappetence,and behavioral changes. As in other species the etiologies offish ocular tumors are not always obvious, but viral disease(e.g., cyprinid herpesvirus 1), excessive ultraviolet lightexposure, parasitism, environmental contaminants, andgenetic predisposition have been implicated in spontaneousneoplasm development in several fish species (Sirri et al.2018; Vergneau-Grosset et al. 2017). Reports in the literaturedocumenting ocular neoplasms specifically include aniridociliary melanoma in a long-horned cowfish Lactoriacornuta and chromatophoroma in koi Cyprinus carpio(DeSilva et al. 2010; Siniard et al. 2019). Biopsy and histo-pathology are important to determine prognosis and a treat-ment plan. Treatment depends on the location and size of thetumor; surgical excision, debulking, or enucleation may beindicated for cases in which the neoplasm is compressing theglobe or interfering with vision.Perhaps the most common location of neoplasm growth isthe cornea. The authors commonly see cases of cornealneoplasms of various types (Bret A. Moore, unpublisheddata). The use of cryosurgery for treatment of ocularneoplasms in piscine patients is an emerging and promisingtechnique. Cryosurgery employs highly localized freezing toinduce destruction, inflammation, vascular stasis, and occlu-sion of diseased tissue including benign, pre-malignant, andmalignant lesions (Rubinsky 2000). In some cases tumorsresolve following a single session of cryotherapy. Theauthors have successfully treated melanophoroma and cor-neal spindle cell tumors in koi with cryosurgery. Based on theauthors’ experience, minimal to zero surgical excision ordebulking is required prior to cryosurgery for ocular masses.The authors prefer a liquid nitrogen storage device and aspray tip with a small aperture attached to a contact piecefor the procedure. Generally, the liquid nitrogen probe isapplied directly to the surface of the corneal mass for30 seconds to 1 minute (Fig. 5.27), with this cycle beingrepeated two to three times in a single cryotherapy session.Fig. 5.25 Chronic anterior uveitis of unknown origin in a fantail goldfish Carassius auratus94 C. A. Parker-Graham et al.The number of freeze-thaw cycles and contact time intervalsare determined by the corneal condition, tumor location, sizeof aperture selected, and tumor type (benign or malignant). Asurface flush with sterile saline after each freeze-thaw cyclehelps detach the liquid nitrogen probe from the surface of thecorneal lesion. Resultant wounds may be left open to heal viasecond intention; the authors apply a thin layer of Manukahoney on the cryotherapy site(s) and treat the patient withsystemic antimicrobials (danofloxacin) and non-steroidalanti-inflammatories (meloxicam) following each cryotherapysession. Figure 5.28 shows complete resolution of a cornealspindle cell tumor in a koi three months following cryother-apy, as well as restoration of the corneal surface. Figure 5.29shows gradual resolution of a corneal melanophoroma in akoi treated with cryotherapy. Possible complications of cryo-surgery such as soft tissue swelling, hemorrhage, and cornealscarring were not observed in any of these cases post-operatively. The authors find that cryotherapy is particularlyuseful in treating corneal neoplasms as the technique issimple, easily administered, portable, and cost effective. Itcan be easily mastered with appropriate guidance and, mostimportantly, side effects are usually predictable and minimal.The RetinaLight induced retinal degeneration is characterized histologi-cally not merely by retinal atrophy but also by iris vascularFig. 5.26 A ruptured right eye in a fantail goldfish Carassius auratus due to an intraocular spindle cell tumor. (Courtesy of the University ofCalifornia Davis, School of Veterinary Medicine, Ophthalmology Service)Fig. 5.27 Liquid nitrogen probe applied to the surface of a corneal mass on a koi Cyprinus carpio. Note the direct contact between the surface of thecorneal mass and the liquid nitrogen probe (a, b)5 Ophthalmology of Osteichthyes: Bony Fish 95engorgement, swelling and liquefaction of posterior corticallens fibers, choroidal engorgement, thinning of the photore-ceptor layer, retinal pigment epithelial cell hypertrophy withfibrosis and mononuclear cell infiltration (Nasisse et al.1989). Diabetic retinopathy in the carp is associated with aretinal endotheliopathy and vitreous vessel development(Yokote 1974). Retina, choroid, and sclera have also beenreported as being infiltrated by trematode larvae, but theinflammatory changes in these cases are slight (Shariff et al.1980) (Fig. 5.30).Ocular Manifestations of Trematode Infectionsin FishParasites are known to possess a variety of adaptations tomaximize their spread and survival. Of these, trematodesbelonging to the family Diplostomidae are collectivelyknown as eye flukes and infections in fish are referred to asdiplostomiasis. Flukes of the genera Diplostomum spp. andTylodelphys spp. are most commonly reported as causes ofdecreased production in aquaculture. These trematodes havea global distribution in freshwater and brackish water habitats(Valtonen and Gibson 1997) and can lead to severe morbidityand even mortality in fish.Diplostomids have a four-host lifecycle, with the final hostbeing piscivorous birds. Adults living in the avian smallintestine lay eggs that are passed via feces into aquatichabitats. Free swimming miracidiae emerge from the eggsto infect aquatic snails of the family Lymnaeidae which act asfirst intermediate hosts (Grobbelaar et al. 2015). Within thesnail, miracidiae migrate to the intestines and liver beforeundergoing asexual reproduction to produce sporocysts andeventually cercariae. Under warm water conditions, cercariaeemerge from the snail hosts and then swim toward the fishsecond intermediate host. Once infected, the cercariaeFig. 5.28 Complete restoration of the cornea surface and curvature in akoi Cyprinus carpio and complete resolution of a corneal spindle celltumor OD three months after the cryotherapy. (a) Pre-cryotherapy of theright eye (OD); (b) 3-month post-cryotherapy of the right eye (OD); (c)Corneal images of both eyes 1-week post-cryotherapy; (d) Cornealimages of both eyes 3 months post-cryotherapy. Scale bar represents250 um96 C. A. Parker-Graham et al.migrate to their preferred organ in the fish—the brain, thevitreous chamber, or the lens depending on the species.There, they develop into metacercariae and wait for the fishhost to be predated on by the avian final host. It is commonfor a single fish to be infected at the same time by multiplespecies of eye flukes (Rellstab et al. 2011). Aberrant migra-tion of cercariae can cause damage to other organs such as thebrain and retina, potentially resulting in acute death when fishare exposed to large numbers of cercariae (Hoffman andHundley 1957). Moreover, overwintering of the parasite inthe fish host results in infected fish becoming more prone towinter stress syndrome and therefore overwintering mortality(Michálková and Ondračková 2014).Many adaptations allow diplostomids to survive and infecthosts. For cercarial spread, diplostomids use the “bet hedg-ing” strategy as cercariae are released over a long period oftime during the warmer months, with released numbersdecreasing over time. This strategy aims to maximize theFig. 5.29 Complete resolution of corneal melanophoroma in a koi Cyprinus carpiotreated with cryotherapy. (a) Before cryotherapy, (b) Right aftercryotherapy, (c) 2 weeks post-cryotherapy, (d) 2 months post-cryotherapy5 Ophthalmology of Osteichthyes: Bony Fish 97probability of cercariae encountering fish hosts by spreadingout the duration of cercarial release. Cercariae are alsoreleased in larger numbers during the day, indicating a likelypreference toward infecting diurnally active fish (Karvonenet al. 20041). Once emerged from the snail host, cercariaerespond to environmental factors such as shadows andcurrents as they swim toward prospective fish hosts (Haasand Haberl 1997). Molecular cues associated with fishepithelia stimulate cercariae to maintain attachment and sub-sequently infect the fish host through the preferred penetra-tion sites of the gills and fin peduncles (Haas et al. 2002).Within the fish host, cercariae again show chemotaxis asthey orient their migration toward the eye based on molecularcues such as melatonin—an indicator for proximity to theretina. Interestingly, migration is not influenced by bloodflow, as cercariae are still able to correctly orient their migra-tion even in decapitated fish cadavers (Haas et al. 2007). Anexperimental model by Ratanarat-Brockelman (1974) foundthat migration into the eye can occur as early as within thesecond hour post-exposure in water bath, with a maximumspeed of 5.1 mm/h. Migration occurs mostly through muscleand connective tissue, although cercariae can also be found inother tissue types including through blood vessels. The cer-carial penetration gland secretes proteinases to digest its paththrough tissue (Moczoń 1994). Lectin activity is also reportedin penetration secretions and this aids with tissue adhesionwhile potentially interfering with the host’s immune defenses(Mikeš and Horák 2001). Mucopolysaccharides and glyco-gen within the cercariae act as energy stores to fuel theirmigration. The high speed with which cercariae migratethrough the fish is beneficial to the parasite’s survival as thefish’s inflammatory response begins comparatively slower ataround 50 minutes post-penetration. With metacercariaremaining un-encysted in the fish host, it is important forthe parasite’s survival to migrate quickly into their target sitesuch as the immune privileged environment of the lens(Ratanarat-Brockelman 1974).Diplostomid infections of fish eyes primarily result incataract formation, although focal areas of retinal and choroi-dal detachment have also been reported (Grobbelaar et al.2015). Blindness subsequently leads to physiologicalchanges in the fish that further predisposes the fish to preda-tion by avian predators. Within the infected fish’s eye,metacercariae can be found un-encysted in the lens andvitreous. They are visible through slit lamp ophthalmoscopyand appear off-white and semi-transparent with an elongatedshape (Moema et al. 2013). For Tylodelphys sp., remainingfree swimming in the fish’s eye is essential for their survivaland spread. At night, they remain in the lower parts of thevitreous chamber to keep the visual axis largely unobstructedand allow the fish to escape from aquatic predators. Duringdaytime when piscivorous birds are most active,metacercariae then migrate to the central part of the vitreouschamber and increase visual obstruction. Despite the loss ofvision however, infected fish do not appear to have a reducedability to forage for food (Stumbo 2017). In addition to thefish host to becoming less able to avoid avian predators,vision loss also results in a loss in crypsis—fish becomedarker in color, making them more conspicuous to predatorswhen contrasted against a light colored background(Seppälä et al. 2005). This combined with increased risk-taking behavior (Ruehle and Poulin 2020) all contribute tothe transmission success of diplostomid metacercariae totheir final avian hosts. An additional adaptation ofdiplostomids is the fact that their complex lifestyle promotesgenetic diversity. The amount of genetic variation present ineach intermediate host increases throughout the diplostomidlife cycle—fish hosts are found to harbor a more geneticallydiverse set of clones than snail hosts. By using multipleintermediate hosts, diplostomids ensure that geneticallydiverse metacercariae can be transmitted onto final hostswhere sexual reproduction occurs and thereby the diversityof their gene pool (Rauch et al. 2005).Although diplostomids are highly adapted to survivingand spreading through their fish hosts, fish are not completelydefenseless in the face of diplostomid infection. There isevidence of developed immunity in fish introduced to anenvironment containing diplostomids (Karvonen et al.20042), as well as inherent genetic resistance in fishFig. 5.30 Subretinal parasite in a rockfish species, associated withmarked hemorrhage, inflammation, and retinal separation. (Courtesy ofthe Comparative Ocular Pathology Laboratory of Wisconsin)98 C. A. Parker-Graham et al.populations (Kalbe and Kurtz 2006). Behaviorally, fish arealso able to sense and escape from areas of high cercariaedensity (Karvonen et al. 20043). In defending againstparasites, the adaptive immune system plays the largestrole. However, the full activation of the adaptive immunesystem requires longer than the 24-hour period by whichcercariae take to infect the lens. Despite this, there is evidenceof other immunological defense mechanisms at play resultingin varied infectivity in different parasite clones (Rauchet al. 2006).The most effective way of treating diplostomid infectionsin fish is by medical treatment with praziquantel (Bader et al.2019). Although this can be a quick treatment for individualcases of diplostomiasis, disease management in large fishpopulations such as those in aquaculture should instead bebased in correct husbandry. As diplostomids are present in awide range of freshwater habitats, the practical aim of hus-bandry measures would be to minimize infection ratesenough to prevent cataract formation and any secondaryproblems associated with blindness. This can include expos-ing captive-bred fish to environments with low levels ofdiplostomid to allow fish to develop resistance and providingfish with sufficient space to avoid cercaria. As infection isdependent on the amount of cercariae released from snails,higher fish stocking densities also result in lower levels ofdiplostomiasis, although other diseases are predisposed indenser populations (Karvonen et al. 2005). Equally, reducingaquatic snails in habitats where fish are kept may reducecercaria loads as well (Karvonen et al. 2006). The definitivetreatment for cataracts is through phacoemulsification, how-ever given the structural hardness of teleost lenses comparedwith those of mammals, phacoemulsification is not an optionfor teleost fish (Whitaker 2001). An attempt in sturgeonshowever has been shown to be successful (Bakal et al.2005). One additional point to note in diplostomiasis in fishis that along with severe ophthalmic complications includinglens and globe rupture is the potential for the increase inconcomitant bacterial infections (Pylkkö et al. 2006).Reducing infection rates may be easier said than donebecause diplostomids are able to adapt to new hostpopulations (Voutilainen et al. 2009), while climate changecan further benefit the transmission of the parasite by increas-ing snail generations with longer summers (Hakalahti et al.2007) and by increasing the duration of cercarial shedding.Rising water temperatures can also result in fish from warmerclimates with higher parasite loads moving into colderhabitats where fish are naturally less resistant to parasites(Blasco-Costa et al. 2014).Diplostomids are a vast family of trematodes that adopt anarray of adaptations for survival and transmission success,including the unique approach of using the lens as an immuneprivileged site. 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Drayer Wildlife Health Center, University of California DavisSchool of Veterinary Medicine, Davis, CA, USADepartment of Medicine and Epidemiology, University of CaliforniaDavis School of Veterinary Medicine, Davis, CA, USASacramento Zoo, Sacramento, CA, USAe-mail: jgjeltema@ucdavis.edu# Springer Nature Switzerland AG 2022F. Montiani-Ferreira et al. (eds.), Wild and Exotic Animal Ophthalmology, https://doi.org/10.1007/978-3-030-71302-7_6107http://crossmark.crossref.org/dialog/?doi=10.1007/978-3-030-71302-7_6&domain=pdfmailto:jgjeltema@ucdavis.eduhttps://doi.org/10.1007/978-3-030-71302-7_6#DOIfrogs and toads (Integrated Taxonomic Information System(ITIS) 2021). Wild amphibian populations are decliningworldwide with many species facing extinction due to habitatloss, spread of infectious diseases, pollution, climate change,and other factors (Alton and Franklin 2017; Fisher and Gar-ner 2020) (International Union for Conservation of Nature(2016) 2021).Amphibians are often kept under human care as householdpets, as laboratory animals, or for exhibition and educationalpurposes. Additionally, zoological institutions may assistconservation efforts by housing assurance populations ofspecies threatened with extinction or for propagation andpopulation recovery through reintroduction efforts. Animalsheld as pets or in zoological facilities are often valued indi-vidually, but can also be managed as collections, where thevalue of the group may supersede the value of a singleindividual. Ophthalmologists are advised to determine thenature of the relationship and intended use of the amphibianwith the owners, keepers, or researchers to determine themost appropriate course of diagnostic, treatment, or manage-ment actions.General Anatomy and Physiologyof AmphibiansAmphibian anatomy and physiology differs significantlyfrom mammals, which most ophthalmologists may be morefamiliar with. In addition, diverse species differences existwithin each order, corresponding to the wide variety ofhabitats used and ecological niches amphibians fill. Uniqueanatomic and physiologic adaptations abound, and over-extrapolation from one species to all amphibians should beavoided. A basic understanding of general amphibian anat-omy and physiology is essential for providing appropriateveterinary care. This chapter provides a general overview ofclinically relevant anatomy and physiology of amphibians inbroad strokes, which are illustrated by specific examples.IntegumentOne of the most important anatomic and physiologicdifferences of amphibians compared to other taxonomicgroups is the structure and function of the skin. Amphibianskin has a thin dermis (Fig. 6.1) with an epidermis that is only1–2 cells thick and serves a variety of physiologic functionsincluding respiration, thermoregulation, fluid balance, andion transport. It also contains granular, mucous, and serousglands that may secrete toxins, antimicrobial peptides,peptides that support wound-healing,and secretions that pro-tect against water loss (Demori et al. 2019). The thin epithe-lium facilitates cutaneous respiration, and active sodiumpotassium channels in keratinocytes produce osmoticgradients for water absorption (Larsen 2021; Campbellet al. 2012). The skin is delicate, prone to injury, susceptibleto rapid water loss, and is sensitive to fluctuations in pH. Theanatomic characteristics that make amphibian skin permeablefor physiologic functions, however, also permit systemicabsorption of many additional compounds. Astute clinicianscan use this feature to their advantage for instituting treatmentor anesthesia. Conversely, it can also lead to inadvertent orunintended systemic absorption of medications and otherchemicals, toxins, or gases with adverse effects.Additional integumentary features may be present includ-ing stacked iridophores beneath the stratum corneum and amineralized “Eberth–Katschenko” layer within the skin ofanurans to conserve water (Azevedo et al. 2005). The anuranthin dermis is not well adhered to the underlying hypodermis,which allows movement of the skin freely over the underly-ing musculoskeletal features. In contrast, it is tightly adheredto the hypodermis in urodeles, and both arrangements haveimplications for surgical management (Wright 2001b).Paratoid (“parotid”) glands (Fig. 6.1) located at thecaudolateral aspect of the head in some species are an areaof skin with specialized and prominent glandular function foremitting defensive or pheromone secretions (Toledo andJared 1995). The specialized pelvic “drink patch” skinlocated at the ventral inguinal region of many speciescontains specialized vasculature and vasotocin-sensitivewater channels for enhanced fluid absorption and is oftenvisually differentiated by its irregular “bumpy” texture(Hasegawa et al. 2003; Parsons and Mobin 1991). Somemale anurans may develop nuptial pads on or near digit I ofthe front feet characterized by hypertrophied skin. This is asecondary sex characteristic used during amplexus (attach-ment of males to females for fertilization of eggs). Manyspecies are also dermatophagous and may normally ingesttheir skin as it sheds (Weldon et al. 1993).Cardiovascular and Respiratory SystemsAmphibians have a three-chambered heart that includes twoatria and one ventricle with varying degrees of inter-atrialfenestration. The lymphatic system is well-developed withpulsatile lymph hearts that beat independently of the heart forlymphatic circulation (Jones et al. 1997). Paired lymph heartsin most anurans are located dorsocranially to the vertebrabeneath the scapulae with additional pairs located lateral tothe dorsal urostyle (post-sacral spine segment) (Jones et al.1992). Lymph sacs with one-way valves serve as storage sitesfor lymph that can be used to modulate circulatory bloodvolume via the lymph hearts (Hedrick et al. 2014). Endolym-phatic sacs that store calcium and which can be appreciatedradiographically, may extend from the inner ear and along the108 J. L. Gjeltemaentire length of the spine in some species (Parsons and Mobin1991).Amphibian respiration occurs via four different routes:cutaneous, buccopharyngeal, pulmonic, and branchial (viagills) often with multiple routes being used simulta-neously (Helmer andWhiteside 2005). The degree of relianceof an amphibian on a particular method of gas exchangevaries by life stage and species adaptation (Maina 1989;Maina 2002). Often, the natural history and anatomy of thespecies can provide clues to a clinician about the primary sitefor gas exchange. Cutaneous gas exchange is considered animportant route in many urodeles and is particularly impor-tant in groups that have reduced lungs or lack them entirely(Wright 2001b; Goniakowska-Witalinska 1980; Bickfordet al. 2008; Nussbaum and Wilkinson 1995). For speciesthat rely heavily upon cutaneous respiration, the epidermismay be vascularized or the animal may have adaptations suchas extensive skin folds or hair-like projections to increasesurface area for more efficient gas exchange (Hutchison et al.1976; Noble 1925). Cutaneous gas exchange is generallymost effective when the skin is moist, which is an importantconsideration during handling or other veterinary procedures.Buccopharyngeal gas exchange via the oral mucosa isfacilitated by gular pumping at the ventral cervical region.Vocal sac extensions that fill with air are used to produceauditory cues for attracting mates and may be a prominentfeature of males in some species. Nares close during gularpumping to direct air from the buccopharyngeal region intothe lungs (if present) for pulmonic respiration (Wright 2001b;Vasilakos et al. 2006). This type of respiration can be distin-guished from gular pumping due to expansion of the coelo-mic region when it occurs and is generally considered a moreFig. 6.1 Integumentary features of anurans: (a) Paratoid gland of amagnificent tree frog (Ranoidea splendida) is indicated by an asterisk,(b) The thin dermis is only loosely adhered to the underlying hypoder-mis as depicted in this Panamanian golden frog (Atelopus zeteki), (c)Pelvic “drink” patch skin is indicated by an arrow in an Amazon milkfrog (Trachycephalus resinifictrix), (d) Hypertrophied nuptial pad of amale American toad (Anaxyrus americanus) is indicated by anarrow head6 Introduction to Ophthalmology of Amphibia 109important method of gas exchange for anurans. Lung struc-ture can range in complexity, with the majority of specieshaving variations of simple unicameral “sac like” lungs(Fig. 6.2) (Herrel et al. 2019; Maina 2002). The left lung isoften reduced or absent in caecilians (Kuehne and Junqueira2000; Maina 2002). Many anurans will inflate their lungsduring handling as a defensive behavior, which can obscurepalpation of the coelomic cavity during examination. Thetrachea is short or non-existent in anurans, which can com-plicate use of endotracheal tubes during clinical procedures(Barbon et al. 2019; Kuehne and Junqueira 2000). Branchialrespiration via gills is typically employed by larval stages ofamphibians and for certain groups of urodeles that retainjuvenile characteristics throughout life. Anurans andcaecilians typically resorb gills before hatch or duringmetamorphosis.Gastrointestinal, Urinary, and ReproductiveSystemsA sphincter separates the oral cavity from esophagus(Fig. 6.2) and some anurans are able to voluntarily everttheir stomach into or even out of the oral cavity to facilitateremoval of undesirable ingesta. Relatively little water istypically absorbed from the intestines, with fluid absorptionacross the skin often serving this function instead (Campbellet al. 2012). There is a cloaca with a common vent openingfor the urinary, gastrointestinal, and reproductive tracts,which is positioned at the end of the animal’s length incaecilians due to the presence of an abbreviated tail.All adult amphibians are carnivorous and have simpleshort gastrointestinal tracts. Teeth are variable in anuransand when present are only located on the maxillary occlusalFig. 6.2 Respiratory and Gastrointestinal features of amphibians: (a)Unicameral “sac like” lungs in an Amazon milk frog (Trachycephalusresinifictrix) indicated by asterisks. Note that the right lung is moreinsufflated than the left lung, (b) The tongue in anurans is positionedwith the distal tip folded caudally within the oral cavity in this smokeyjungle frog (Leptodactylus pentadactylus), (c) A sphincter separating theoral cavity from the esophagus is located just dorsal to the intubatedglottis in this smoky jungle frog110 J. L. Gjeltemasurface. Both mandibular and maxillary teeth are generallypresent in urodeles and caecilians with some species of thelatter group also having venom glands along the teeth(Mailho-Fontana et al. 2020). The tongue (Fig. 6.2) in mostanurans is situated with the distal tip folded caudally withinthe oral cavityThe perfection of the eye and the perception of light is athing of beauty. From one animal to the next, this beauty isexemplified in unlimited displays, as nature once again natu-rally captivates us humans from early childhood. The perfectbalance of simpleness and complexity that makes up thevisual system so seamlessly fits the needs of each individualanimal, from the small insect to the giants of the sea. Thatbalance is in such harmony and is so delicate, that even asubtle anatomical or physiologic change can render the eyeuseless and can mean an end of life for the individualinvolved. As we dive into the eye, perhaps a good place tostart is far away from our personal experience of vision, andfar away from the animals that we interact with day by day.Rather, we should dive into a little pond and look under amicroscope where we might find two organisms, Euglena(Fig. 1.1a) and Chlamydomonas (Fig. 1.1b). These unicellu-lar protists both have an obvious orange-colored eyespot butin other ways they are quite different. Euglena gracilis is aphotosynthesising autotroph although at low light intensitiesit can survive as a heterotroph by ingesting plant material. Itis in reality neither strictly plant nor animal but ratheroccupies a third kingdom as a protist. Chlamydomonarheinhartiiis can perhaps be more strictly defined as a greenalga in the plant kingdom. Phototaxis is vital for bothorganisms, allowing them to move toward light given thatthey depend on light for energy and nutrition. Yet they alsoexhibit negative phototaxis when protecting themselvesagainst light when illumination becomes too intense. Thecarotenoid accretion is called the eyespot but truth be told itis not the photoreceptor itself. Rather it acts to shade thephotoreceptor from light from one direction. Thisdemonstrates the essential components of any visual system;any photosensitive organism needs a photoreceptor thatdetects the light. But that alone would not allow the organismto determine the direction of the light source. A pigment spotreduces the illumination from one direction or changes thewavelength of the incident light falling on the photoreceptor,thus allowing the organism to move toward the direction ofthe light or away for it. Thirdly a mechanism to promotemovement is essential. To detect the light is one thing but toD. L. Williams (*)Department of Veterinary Medicine, University of Cambridge,Cambridge, UKe-mail: dlw33@cam.ac.uk# Springer Nature Switzerland AG 2022F. Montiani-Ferreira et al. (eds.), Wild and Exotic Animal Ophthalmology, https://doi.org/10.1007/978-3-030-71302-7_13http://crossmark.crossref.org/dialog/?doi=10.1007/978-3-030-71302-7_1&domain=pdfmailto:dlw33@cam.ac.ukhttps://doi.org/10.1007/978-3-030-71302-7_1#DOImove toward or away from it requires a motor system; theflagellae in Chlamydomonas and Euglena. A mechanism isalso required by which detection of light can be translatedinto a change in flagellar movement, generally an ion flux ofsome kind.In Euglena the photoreceptor, a tightly packed mass ofcrystalline protein, is located next to the eyespot (Fig. 1.2a). Ithas been estimated that the photoreceptor contains around2� 107 molecules of a rhodopsin-like protein (Gualtieri et al.1992). Around 108 photons impinging on this crystal saturatethe protein with a maximum absorption at around500–525 nm (Barsanti et al. 1997, 2000). Photo-stimulationleads to positive phototaxis with the ion flux giving whatsurprisingly appears like an electroretinogram (Fig. 1.2b)!In Chlamydomonas, the eyespot apparatus consists ofthylakoid membranes with layers of carotenoid-rich globulesand photoreceptor molecules in the membranes betweenthese globules. Chlamydomonas has a flavin-associatedblue-sensitive chromophore, (Forbes-Stovall et al. 2014)highly sensitive to blue light at a wavelength of 440 nm,and intimately linked to its circadian clock. Although thisalgal species is essentially a plant, genetic analysis of thechromophore shows what has previously been considered ananimal chromophore CRY2 (Mittag et al. 2005). Indeed,CRY1 and CRY2 have been detected in light-sensitive gan-glion cells in the human retina responsible for pupillary lightreactivity and setting of photocycles (Bouly et al. 2007).How nice it would be to see these two organisms asforerunners of both the rhodopsin-based photo-detectionsystems of mammalian rod and cone photoreceptors andprecursors of the more recently discovered blue wavelengthdetection systems in light-sensitive ganglion cells. Nonethe-less, evolution is never as simple as that. For a start, each ofthese organisms has multiple light-detecting molecules.Euglena orientates itself toward light using a rhodopsinphotopigment, but also has a blue light receptor (Häder andFig. 1.1 (a) Euglena, (b) Chlamydomonas (600� magnification). Used with permission from Williams (2016)PCa b10 msecFCexcitationflashFig. 1.2 (a) Euglenaphotoreceptor rhodopsin crystalpositioned next to emergentflagellum after Barsanti et al.(2012). (b) Euglenaelectroretinogram measuring thephotoelectric effect of thephotoreceptor of Euglena gracilisafter Nichols and Rikmenspoel(1977). Used with permissionfrom Williams (2016)4 D. L. WilliamsLebert 2009). The photo-reorientation of the organism awayfrom light is modulated through increased levels of cyclicAMP produced by a blue-light-activated adenylyl cyclase(PAC) (Koumura et al. 2004; Iseki et al. 2002). Similarly,while negative phototaxis in Chlamydomonasis is modulatedby PAC, photoattraction occurs through the action of twosensory rhodopsins CSRA and CSRB discovered bySineshchekov and colleagues in 2002, also called channelrhodopsins, ChR1 and ChR2 by Nagel’s group (Nagel et al.2002), and termed Acop1 by Suzuki and colleagues (Suzukiet al. 2003). The two photoreceptor proteins have differentabsorption profiles with CSRA absorbing predominantly atblue-green wavelengths and promoting a photophobicresponse in response to strong illumination while CSRBabsorbs at shorter wavelengths and leads to phototaxis atweaker light intensities (Sineshchekov and Spudich 2005).There are around 9 � 104 molecules of CSRA and 1.5 � 104molecules of CSRB in each cell (Sineshchekov et al. 2009).ChR2 is a photoactivated cation channel but in addition actsas a light-driven proton pump. While this double action mightseem somewhat perverse it is not unique—other chloridechannels also act as proton pumps, demonstrating their originas Cl�/H+ exchangers. But the ChRs do not exhibit homol-ogy with other ion channels but rather with rhodopsins.Indeed, these photoactive ion channels did not start theirevolutionary existence in the Euglenoids andChlamydomonads we have been discussing above. Sucheukaryotes originated probably between 800 and 1200 mil-lion years ago (Knoll 2014) but prokaryotes have been pres-ent in the fossil record around 1500 million years earlier(Cavalier-Smith 2006). Lynn Margulis presented the theoryby which eukaryotes formed through endophagy of prokary-ote algae to produce chloroplasts and bacteria to yieldmitochondria, both examples of endosymbiosis (Margulis1970). So, we should look for the origin of these eukaryotephotopigments in prokaryote bacteria (Pertseva and Shpakov2009).Photopigment OriginsThe photoresponsive prokaryotes to investigate are boththose which are photosynthetic such as Synechocystis andthose like Halobacterium which are not. Halobacterium spe-cies (Bibikov et al. 1991; Marwan et al. 1995) have fourphotosensory proteins; Bacteriorhodopsin (BR) a protonpump, Halorhodopsin (HR) a light-gated chloride pump,and two sensory rhodopsins. Each acts as photoreceptorsbut BR, existing in much higher copy number than theother proteins, can act on its own as shown by producingblind mutants and recovering photosensitivity byreconstituting BR alone (Bibikov et al. 1993). BR is a purplemolecule, with an absorptionand can be fixed in position for caecilians. Itplays an important role in feeding mechanisms for mostanurans (Herrel et al. 2019). In many anurans, only a thinlayer of soft tissue separates the roof of the mouth from theocular globes. The globes can be voluntarily retracted (Fig. 6.3)and retropulsed to cause protrusion of the globe into the oralcavity and may serve to push food into the caudal pharynx andesophagus during swallowing in some species. Manyamphibians are indiscriminate eaters and may inadvertentlyingest foreign objects near prey or may experience gastricoverload and subsequent impaction due to overindulgence.Fig. 6.3 Intraoral retraction of ocular globe in anurans: Only a thinlayer of soft tissue separates the roof of the mouth from the ocular globesin many anurans. The globes may be retracted and retropulsed to causeprotrusion of the globe into the oral cavity. This may serve to push foodinto the caudal pharynx during swallowing. (a) Eyes open in a smokyjungle frog (Leptodactylus pentadactylus), (b) Eyes closed with partialretraction of the ocular globe in a smoky jungle frog, (c) Intraoral viewof the dorsal oral cavity of a blue-legged mantella frog (Mantellaexpectata) with eyes open. (d) Intraoral view of the dorsal oral cavityof the same blue-legged mantella frog with eyes closed and globesprotruding into the oral cavity6 Introduction to Ophthalmology of Amphibia 111Amphibians may secrete nitrogenous waste as ammonia,urea, or uric acid depending on adaptations related to naturalhistory and environmental conditions. Kidneys are meso-nephric and do not include a loop of Henle for concentrationof urine. Urinary bladders may serve as a reservoir for waterin some species (Campbell et al. 2012). A renal-portal systemis present with blood passing from the hindlimbs through thekidneys before entering systemic circulation (Wright 2001b;Maina 2002). This should be considered when administeringpotentially nephrotoxic medications and those that are pri-marily cleared by the kidneys, although the clinical impor-tance of this anatomic feature remains unclear at this time.Musculoskeletal SystemThe axial skeleton of anurans is composed of three segments(pre-sacral, sacral, and post-sacral) that each contain fusedvertebrae. The post-sacral segment is referred to as the uro-style and the ribs at the pre-sacral segment are short. The tibiaand fibula as well as the radius and ulna are fused (Wright2001b). The vertebrae in urodeles is not fused and lacks thedefined segmentation that is seen in anurans. Caecilians lackpectoral and pelvic girdles, completely.Sensory OrgansVision and sight play an important role in feeding behavior ofmany amphibians; thus, its management is critically impor-tant to an animal’s overall health and welfare and is particu-larly important in terrestrial anuran species. Blind anuransoften become anorexic due to lack of sight-related feedingcues, and long-term support with assisted feeding effortsoften raises concerns for an animal’s overall quality of life.Urodeles and aquatic anurans may rely more heavily uponolfactory senses in addition to vision for feeding and may beable to cope better with vision deficits (Jørgensen 2007).Caecilian species rely primarily on olfactory cues and havetentacles at the rostrum to serve this function (Baitchman andHerman 2015). Sight plays a minimal role in feeding behav-ior for caecilians with most species having small eyes thatmay be covered with skin and have limited or reduced sen-sory capability compared to other amphibians. Aquatic larvaeand adults may also have lateral lines along the body thatfunction to sense water currents and movement.Metamorphosis and NeotenyLarval (tadpole) stages of amphibians are primarily aquatic.They are generally herbivorous or omnivorous and lackkeratinized skin with the exception of the mouth parts.Lungs, if present, may serve the primary function ofbuoyancy with respiration and excretion of nitrogenouswaste in the form of ammonia via gills. Amphibians transi-tion between their larval stage to their adult form byundergoing metamorphosis. Numerous changes includingthe growth of legs, tail resorption, loss of gills, and formationor development of lungs occurs during this process.Metamorphosis is mediated by the thyroid and has beentriggered by administration of TSH, iodine, and thyroidhormones in various amphibian species (Wakahara 1996;Ingram 1929). Some urodeles exhibit neoteny, maturing toa reproductive stage without undergoing the normal processof metamorphosis for adult life; thus retaining juvenile phys-ical characteristics as adults. Neoteny may be obligate (theanimal never undergoes metamorphosis), inducible (meta-morphosis does not occur naturally, but can occur in responseto thyroid stimulation), and facultative (occurs in response tospecific environmental cues) (Wakahara 1996).Pre-metamorphic larval amphibians and adults of neotenicspecies have regeneration potential, and may regrow digits,limbs, tails, ocular lenses, retinas, heart ventricles, and otherorgans (Brockes 1997; Straube and Tanaka 2006). This is aclinically relevant feature that may be capitalized upon by aclinician during management of specific clinical cases.Husbandry and CareInappropriate husbandry is a frequent cause of ocular andother diseases in amphibians under human care, and a thor-ough evaluation of the environment, diet, and care routine isan important component of the veterinary assessment anddiagnostic process. Careful evaluation of humidity, ultravio-let light levels, temperature, substrate, diet, and water qualityshould be made in reference to known ideal husbandryparameters or based on knowledge of the natural historyand preferred microhabitats for the species. Animal keepers,curatorial staff, and their networks of professional colleaguescan often be helpful for locating species-specificrecommendations when other sources of reliable informationare scarce.Amphibians are ectothermic and normal physiologic func-tion, including an appropriate immune response, metabolism,and healing may be compromised if an amphibian is not keptwithin its preferred optimal temperature zone (Raffel et al.2006; Maniero and Carey 1997). It is also important to notethat many amphibian species are sensitive to thermal stress,and contrary to recommendations for other ectothermicgroups like reptiles, many critically ill amphibians benefitby being kept at the cooler rather than the warmer end oftheir optimal temperature zone (Chai 2015).Water quality is another important environmental factor toconsider for all amphibians, especially for aquatic species,and should be tested regularly. Chlorinated water (such asthat from municipal sources) should not be used in enclosures112 J. L. Gjeltemaor for handling. Some types of water (reverse osmosis anddistilled) require re-constitution with electrolytes prior tolong-term use. Due to the rapid loss of water that can occurthrough amphibian skin and the lack of urinary concentratingability, appropriate humidity is essential to maintain hydra-tion and ideal health. Appropriate ultraviolet light conditions,length of exposure, appropriate stocking density, and optionsfor shade are essential for preventing a variety of diseasesincluding nutritional secondary hyperparathyroidism,cataracts, burns, and development of dermal neoplasia.Reared prey, like crickets, fruit flies, pinkies, and mice,typically make up the bulk of the diet of most amphibians andis unlikely to provide the same diverse nutrient profile of wildamphibian diets. Gut-loading is a method of providing keynutrients to an amphibian by managing the prey item’s dietprior ingestion by the amphibian. Nutrients of particularconcern to amphibian ophthalmologic health include lipid,calcium, vitamin D, and vitamin A (Chai 2015).The enclosure substrate and accoutrement are also rele-vant as they posemaximum in greenwavelengths, hyperpolarizing the cell membrane at around570 nm while HR absorbs at green-yellow wavelengths,depolarising the membrane. The BR gene has limitedsequence homology with other photoreceptive rhodopsinssuch as those in mammalian rod photoreceptors (Pertsevaand Shpakov 2009), but it does have the structural similaritiesof the seven transmembrane domains (Spudich 1993) and aprotonated Lys-216 Schiff base where the prosthetic group ofretinal binds. The big difference is that while eukaryoterhodopsins are associated with a G protein (Palczewski2006), prokaryote rhodopsins are not. It had been consideredthat eukaryote and prokaryote rhodopsins were a primeexample of evolutionary convergence (Lamb 2013) but struc-tural homologies have shown that these apparently differentamino acid sequences are indeed formed through classicevolutionary divergence from a common ancestor (Mackinet al. 2014; Shen et al. 2013).A completely different prokaryote class is cyanobacteria.They have a number of photoreceptor molecules(Montgomery 2007; Ikeuchi and Ishizuka 2008) fromphytochromes like RcaE (the regulator of chromatic adapta-tion) in Fremyelia, to Cph-1 a light-regulated biliproteinkinase absorbing in the far red. Blue light photosensorswith a conserved flavin-bound BLUF (blue light usingFAD) domain illustrate the diversity of wavelengthsabsorbed by these photochromes. We like to think that ashumans we have a highly developed sense of color vision buteven these cyanobacteria are able to detect light of differentwavelengths (Kehoe 2010). Why should these primitiveorganisms need such a complex system of chromatic detec-tion? Cyanobacteria live in water columns which at thesurface are illuminated by light of a wide variety ofwavelengths but at depth blue light predominates. Thus,cyanobacteria migrating up and down a water column expe-rience a far greater range of background color compared totheir land-based plant relatives, and differential sensitivity toa variety of wavelengths has evolved.The problem here is that even as far back as theprokaryotes the complex seven transmembrane domainarrangement of opsin molecules seems to prevail withoutsimpler photoreceptors existing concurrently. Darwin’s orig-inal puzzle over ocular evolution seems still to be with us butnow at a molecular level. Having said that, investigation ofopsin diversity sheds considerable light on the evolution oflife once we get beyond the protist stage. As Eakin suggestedover 50 years ago (Eakin 1963), there are two evolutionarylines of photoreceptors, those involving animals with photo-sensitive cilia and those with rhabdomeres. The latter are theProtostomia including the arthropods while the former are theDeuterostomes which include the vertebrates. They havedifferent opsins (R and C) and different mechanisms ofconverting light signals to nerve impulses; C opsins function-ing through a cyclic nucleotide pathway while R opsins use1 Evolution of Photoreception and the Eye 5phospholipase C for signal transduction. Two unusualorganisms, Amphioxus and Platyneris have eyes using ciliaryopsins and others with rhabdomeric opsins, putting them inan interesting transitional position between the arthropodrhabdomeric photoreceptors and the vertebrate’s ciliaryphotoreceptors. Amphioxus, the lancelet, found half-buriedin sand across the world, is a protovertebrate, having anotochord but no true spine. It has rhabdomericphotoreceptors but also lateral eyes with ciliaryphotoreceptors (Koyanagi et al. 2005). The opsin in thesecells is the Amphioxus homolog of melanopsin, coupled withGq as are invertebrate rhodopsins (Koyanagi and Terakita2008). Platyneris is a polychaete worm found living inmarine kelp beds. Although clearly an invertebrate witheyes using rhabdomeric opsin, it also has structures withinthe brain with a ciliary photoreceptor and vertebrate-typeopsin (Arendt et al. 2004), specifically melanopsin, centralto mammalian light-sensitive retinal ganglion cell function(Sexton et al. 2012).It might be wondered why we have spent so much timediscussing the evolution of photoreception in invertebratesbefore moving on to discussing details of either invertebrateor vertebrate eyes, beginning with the vision and eyes ofjawless fish. 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Proc Natl Acad Sci U S A 99:8689–8694Sineshchekov OA, Govorunova EG, Spudich JL (2009) Photosensoryfunctions of channelrhodopsins in native algal cells. PhotochemPhotobiol 85:556–563Spudich JL (1993) Color sensing in the archaea: a eukaryotic-likereceptor coupled to a prokaryotic transducer. J Bacteriol 175:7755–7761Suzuki T, Yamasaki K, Fujita S et al (2003) Archaeal-type rhodopsins inChlamydomonas: model structure and intracellular localization.Biochem Biophys Res Commun 301:711–717Williams DL (2016) Light and the evolution of vision. Eye 30(2):173–178Zhao F, Bottjer DJ, Hu S et al (2013) Complexity and diversity of eyesin early Cambrian ecosystems. Sci Rep 3:27511 Evolution of Photoreception and the Eye 7Ophthalmology of Invertebrates 2Jenessa L. Gjeltema, Kate S. Freeman, and Gregory A. Lewbart# Chrisoula SkouritakisJ. L. Gjeltema (*)Department of Medicine and Epidemiology and the Karen C. DrayerWildlife Health Center, University of California Davis School ofVeterinary Medicine, Davis, CA, USAe-mail: jgjeltema@ucdavis.eduK. S. FreemanDepartment of Clinical Sciences, College of Veterinary Medicine andBiomedical Sciences, Colorado State University, Fort Collins, CO,USAG. A. LewbartDepartment of Clinical Sciences, North Carolina State UniversityCollege of Veterinary Medicine, Raleigh, NC, USA# Springer Nature Switzerland AG 2022F. Montiani-Ferreira et al. (eds.), Wild and Exotic Animal Ophthalmology, https://doi.org/10.1007/978-3-030-71302-7_29http://crossmark.crossref.org/dialog/?doi=10.1007/978-3-030-71302-7_2&domain=pdfmailto:jgjeltema@ucdavis.eduhttps://doi.org/10.1007/978-3-030-71302-7_2#DOIIntroductionInvertebrate Diversity and MedicineInvertebrates are an expansive and diverse group of animalsthat account for over 95% of the living animal species onEarth. In addition to multicellularity, the key distinguishingcharacteristic of this broad group is the lack of a vertebralcolumn. Invertebrates vary widely in their anatomic structure,complexity, physiology, size, and ecological niches. Classifi-cation is traditionally based on characteristics includingdegree of tissue organization, symmetry, degree of bodycavity development, presence of an exoskeleton, andsegmentation.Invertebrate medicine has been a historically neglectedfield within the veterinary profession, with the vast majorityof veterinary research on invertebrates being focused onparasites affecting vertebrate species. Although there is agrowing body of literature on invertebrate medicine in cur-rent veterinary scientific publications, research from the fieldsof entomology, physiology, parasitology, zoology, biology,and ecology comprise a much larger and significant source ofour current understanding of invertebrate health.With increasing recognition of invertebrates as havingimportant ecological, agricultural, research, and economicroles that benefit from veterinary attention, there has been agrowing demand for consultation with veterinarians on thehealth, conservation, and welfare of invertebrate animals.Clinicians wishing to develop knowledge and skills in inver-tebrate medicine are encouraged to explore literature andprofessional networks both within and outside the field ofveterinary medicine to develop proficiency and expertise. Abroader review and discussion of veterinary clinicaltechniques and diseases of invertebrates is available else-where for the interested clinician (Lewbart 2022). Due tothe diversity of invertebrates, clinicians are encouraged toseek out additional resources when working with an inverte-brate that they are less familiar with.While not all invertebrates have eyes, groups that possessadaptations for vision warrant discussion. This chapter servesto orient and introduces ophthalmologists and veterinarianscaring for invertebrates to the natural history, anatomy, andclinical techniques available for evaluation and medical treat-ment of several diverse invertebrate groups, with hopes that itserves as a platform for future growth in our understandingand in the available medical care of these animals.Early Sight and VisionThe diversity of invertebrate eyes paints a picture of the earlydevelopment of vision. This evolution can be divided intofour basic stages as outlined in Fig. 2.1: (1) nondirectionalphotoreception, (2) directional photoreception, (3) spatialvision with low resolution, and (4) spatial vision with highresolution (Nilsson 2013). Photoreceptor cells are thought tohave evolved during the Precambrian Period around 600–800million years ago allowing simple nondirectional photorecep-tion. Adaptations of membrane stacking for directional pho-toreception emerged next.Depending on the primary membrane used for photore-ception, receptors can be classified as either rhabdomeric(using microvilli) or ciliary (using cilia) (Eakin 1965).Invertebrates of protostome (mouth-first development)Fig. 2.1 Four stages of the evolution of vision from nondirectionalphotoreception to high-resolution spatial vision. Compound eyes aredemonstrated to be principally different from single-chambered eyes,which suggests divergence from more primitive photoreceptivestructures. Used with permission from “Nilsson (2013). Eye evolutionand its functional basis. Visual Neuroscience, 30, 5–20”10 J. L. Gjeltema et al.lineage generallydevelop rhabdomeric photoreceptors whileanimals with deuterostome (anus-first, mouth-second) devel-opment generally have ciliary photoreceptors. Crustaceans,insects, spiders, squids, snails, and worms all haverhabdomeric photoreception. Sea urchins, starfish, andchordates including vertebrates have ciliary photoreception.The first “eyes” consisting of aggregates of recessedphotoreceptors with an aperture occurred at the beginningof the Cambrian Period around 540 million years ago(Michael F. Land 2018). These eyes allow for spatial visionwith low resolution and can be divided into two majorgroups: single-chambered eyes and multi-chambered com-pound eyes (see Fig. 2.1). Due to the limited number ofways that light can be manipulated, the optics for both singlechamber and compound eyes can be categorized into threebasic types: simple shadowing, use of lenses, or use ofmirrors. Based on this, eight different types of eyes haveevolved and are known to exist in animals and are outlinedand depicted in Fig. 2.2 (Michael F. Land 2018).Simple shadowing with either a simple pinhole eye or asimple compound eye provides low-resolution spatial vision.Invertebrate groups that have this type of vision includeNematoda, Onchyophora, Platyzoa, Bivalvia, Gastropoda,Polychaeta, and Echinodermata. Optical adaptations usinglenses, corneas, and mirrors in both single-chamber and com-pound eyes have led to separate adaptations for spatial visionwith high resolution. This higher resolution spatial vision canbe found in invertebrate arthropods (insects, crustaceans, andspiders) and cephalopods (octopuses and squids) as well asvertebrates. It is important to note that processing, use, andinterpretation of information gained via sight also relies uponneuroanatomic adaptations in addition to ocular anatomy.Animal groups with eyes adapted for high-resolution spatialvision also have a large portion of the brain devoted to thissensory system. The phylogenetic relationships ofinvertebrates and the predominant vision type for eachgroup are summarized in Fig. 2.3 (Nilsson 2013).The remainder of this chapter will highlight specific inver-tebrate adaptations of particular interest to the ophthalmolo-gist as well as provide basic information related to handlingand clinical techniques commonly used for the groupsdiscussed. It is our hope that the information in this chapterwill provide ophthalmologists inspiration and a practicalfoundation for further exploration and involvement in thefield of invertebrate medicine.CEPHALOPODAIntroduction and Natural HistoryThe class Cephalopoda in the phylum Mollusca includessquids, octopuses, cuttlefish, and nautiluses. The word ceph-alopod is of Greek origin and means “head foot,” which is areference to a key feature of this group—the head directlyattached to the many arms. All extant species are part of thesubclass Coleoidea, with the exception of the Nautilus.Within the Coleoidea, there are three orders: Sepioidea(cuttlefishes and the bottle-tailed squid), Teuthoidea (allother squids), and Octopoda (octopuses).Cephalopods range widely in size with the giant squid(Architeuthis dux) measuring longer than a school bus andabSimple pinholeeyeCorneal eye Lens eye Concave mirror eyeReflectingsuperposition eyeRefractingsuperposition eyeAppositioneyeSimple compoundeyed cghfeFig. 2.2 The eight principal types of eyes known in animals. Used with permission from “Land (2018). Eyes to see: The astonishing variety ofvision in nature (First edition). Oxford University Press”2 Ophthalmology of Invertebrates 11some of the octopuses and southern pygmy squid(Xipholeptos notoides) measuring only an inch in totallength. The general external anatomy of the cephalopodincludes the head, eyes, mantle, siphon, and arms. Movementis achieved by relaxation and contraction of muscles in themantle, which expels water and propels the animal in theopposing direction. The animals can also “hover” or maintainneutral buoyancy by either moving fins located on the mantle(cuttlefish and some squid) or via chemical buoyancy withammonia (Clements et al. 2017).Species in Coleoidea have internalized shells that form a“pen” or “gladius” and a basic organization with 8 arms.Cuttlefish and squid, however, have 2 additional armswhich are called tentacles. Arms and tentacles may havesuckers on their surface which are used to grab prey and,particularly with octopuses, aid in mobility by forming a tightseal for excellent grip. The nautiluses differ from theColeoidea in that they have an external shell and have up to90 or more arms referred to as “cirri” that differ in number byspecies. The cirri do not have suckers, but instead, havesticky grooves for prey capture.The circulatory system includes multiple hearts, two ofwhich distribute deoxygenated blood-like hemolymph togills and one of which pumps oxygen-rich hemolymph tothe rest of the body. The hemolymph is blue in appearance asit uses copper (hemocyanin) for oxygen storage rather thaniron as in vertebrates. Nautiluses are unique in their oxygenstoring ability and are capable of diving to extreme depths of700 m, markedly lowering their metabolic rate to require lessoxygen, and can use oxygen stored in their shells during theseperiods (Redmond 2010).Cephalopods have a fast growth rate until sexual maturity,after which it slows down markedly. Once sexual maturity isreached, many species spawn, undergo “senescence,” and diesoon thereafter (Anderson et al. 2002). Fertilization occurs bydirect mating. Unlike other mollusks, they do not have aFig. 2.3 Phylogenetic tree showing the diversity of vision in invertebrate groups. Used with permission from “Nilsson (2013). Eye evolution and itsfunctional basis. Visual Neuroscience, 30, 5–20”12 J. L. Gjeltema et al.larval life stage although there is a juvenile planktonic stage.They are carnivorous and consume a variety of prey includ-ing fish, jellies, crustaceans, bivalves, and other cephalopods.Many have a rigid beak designed to crush or open shelledprey items. In addition to humans, cephalopods are preyedupon by marine mammals, birds, and some eels. One of themost well-known and celebrated facts about cephalopods isthat they can be highly intelligent, may hide remarkably wellby using skin chromatophores for camouflage, can opentoddler-proof jars, have unique personalities, and can squeezethemselves into the narrowest of escape routes.HandlingMost species within this group of invertebrates can be cap-tured by hand or carefully with nets. Some species kept underhuman care, like octopuses, can be quite strong, intelligent,dexterous, slippery, and fragile, which can make handlingthem a challenge. Suckers can easily attach to the skin of ahandler and strong beaks used to crush the shells of prey canpotentially inflict serious injuries. For this reason, soft clothhandling gloves that protect and prevent suctioning to theskin are needed when handling this group of invertebrates.Many species are incredibly intelligent and can be trainedusing food (such as fish) as a motivator for voluntary partici-pation in some veterinary evaluations.While all octopuses, cuttlefish, and some squid, are ven-omous, only some are acutely deadly. Some species like theblue-ringed octopus (Hapalochlaena spp.) produces a potentlethal neurotoxin that contains tetrodotoxin and will kill ahuman within minutes if bitten. These animals should not bemanually restrained. Cephalopods are often upset anddisrupted by handling; they may release ink into the waterwhen stressed and may refuse to move for some time after ahandling event. To minimize stress, examination ofcephalopods in their main living environment should beconsidered when possible and appropriate. The animal canbe gently lifted to the surface with aid of a net positionedunder it to maintain partial submergence under the waterduring evaluation.Care should be taken to prevent the animalfrom grasping and submerging sensitive equipment with itsmany dexterous arms.Several effective anesthetic techniques have been reportedin cephalopods including the use of magnesium chloride,ethanol, and isoflurane anesthetic baths and may be consid-ered for conducting invasive procedures or when manualrestraint is not feasible or appropriate (Yang et al. 2020)(Harms et al. 2006) (Polese et al. 2014) (Roumbedakis et al.2020).Clinical TechniquesThe ophthalmic exam can be performed as with other speciesusing a slit lamp biomicroscope, tonometer (rebound pre-ferred), fluorescein staining, and indirect ophthalmoscopy.For using a slit lamp, since the cephalopod will ideally stillbe submerged with just the eye exposed, a waterproof pro-tective cover over at least the bottom of the slit lamp is ideal.While topical or targeted oral treatments may be possiblein some cases, treating the water in the tank or via bath maybe an easier option. For any tank-based treatments, the impactof the treatment on other species in the enclosure as well asthe bacteria of the biofilter are important factors to consider.Very limited evidence-based and clinically-oriented scientificreports are available in the veterinary literature describingcase management or interventional treatments forcephalopods (Gore et al. 2005) (Harms et al. 2006).Whenever there is a medical concern such as cornealopacification, particularly if multiple animals are affected, itis important to evaluate water quality. In some species, evensmall fluctuations in water quality parameters can affectanimal health. Multiple organ systems may be impacted,and often an effect on the cornea is noticed first. In thesecases, correcting the water quality is the best way to treat thecondition.Ophthalmologic Anatomy and PhysiologyOrbit, Globe, and AdnexaThe eyes of cephalopods are located bilaterally on the headand are generally very well developed with adaptations forspatial vision with high resolution. Cephalopod eyes havebeen compared to human eyes and the comparison is notincorrect since both share a single-chamber structure. Thereis a shared gene (Pax6) that controls embryologic eye devel-opment that is similar in humans and cephalopods (Gehring2004). Debate continues about whether this is an example ofconvergent or parallel evolution with a common ancestor.There are several important differences between octopods,like the octopus, and decapods, like squid. The octopus hasseven extraocular muscles and seven corresponding nerves(Budelmann and Young 1984). This is in contrast to thedecapods who are reported to have between twelve and four-teen extraocular muscles (species dependent), which areinnervated by only 4 nerves and are responsible for convergenteye movement (Thore 1939) (Hilig 1912) (Glockauer 1915)(Budelmann and Young 1993). These muscle differences areresponsible for the more monocular vision of octopods2 Ophthalmology of Invertebrates 13compared to binocular vision of decapods. There are alsosome extraocular muscle differences between groups ofdecapods. For example, squids (Loligo and Sepioteuthiszspp.) have a significant and powerful anterior muscle whichis not present in the eyes of cuttlefish (Sepia spp.). Decapodsalso have a trochlear cartilage and membrane septum thatattaches to the anterior-medial globe (Budelmann and Young1993). Some of the extraocular muscles insert onto this carti-lage and it is involved in ocular movements. For decapods,there are no specific adnexal structures as typically defined fora vertebrate eye. The eye is nestled within the soft tissues andthere is no conjunctiva, eyelid, nasolacrimal system, or sclera.Most octopods have a two-part cornea with an uppertransparent lid that overlaps a lower transparent lid. Not allcephalopods have a cornea and squids vary in this anatomicfeature. A corneal covering is present in the suborderMyopsida and absent in Oregopsida. The cornea in Myopsidaspecies is similar to an extension of an eyelid but is clear andthere are actually no functional eyelids. In species withoutcorneas, the lens is exposed directly to external seawater andthe eyelids can close and are transparent. Figure 2.4 providesan excellent view of the cornea from the side (as well as theiris and lens). The nautilus lacks both a cornea and a lens(Fig. 2.4b).Fig. 2.4 General differences in eye structure between an octopus (a)and a chambered nautilus Nautilus pompilius (b). (a) Side view of theanterior segment of an octopus clearly showing the cornea, iris, and lens.A Chambered nautilus eye in cross-section (b) and histologic cross-section (c) demonstrating the absent cornea, the pinhole pupil, aphakia(no lens), and vitreous chamber. (a)—Courtesy of David G.Heidemann. (b, c)—Courtesy of the Comparative Ocular PathologyLaboratory of Wisconsin14 J. L. Gjeltema et al.Uvea and LensThe pupil shape differs between the different orders ofcephalopods with octopuses having an ovoid to rectangularpupil (Fig. 2.5 a, b), squid having a circular to slightly ovoidpupil (Fig. 2.5c), and cuttlefish having a w-shaped pupil(Fig. 2.5d). The pupil of the octopus is always in the horizon-tal plane, regardless of the orientation of the octopus and ismaintained in this position by the autonomic nervous system.The maintenance of pupil shape and orientation is performedby a statocyst, a sensory organ that is similar in function tothe inner ear components of vertebrates and includes endo-lymph and hair cells. The statocyst controls the extraocularmuscles (Cobb and Williamson 1999). The nautilus has themost basic eye structure of this group of animals with acircular pupil whose iris can dilate and constrict, but thatlacks a lens.For most cephalopods, the lens is spherical and may ormay not be exposed to seawater depending on the species.One study of cuttlefish found that its lens is developed in aunique way with a plate-like configuration as seen by scan-ning electron microscopy at the anterior and posterior halveswith fiber-like extensions at the periphery (Willekens et al.1984). The lens appearance and wavelength sensitivity ofcephalopods vary based on animal habitat with surface-dwelling squid having yellow-appearing lenses which refractFig. 2.5 Pupil shape in species of Cephalopoda. (a) Horizontal ovoidand (b) horizontal rectangular-shaped pupil of a coconut octopusAmphioctopus marginatus. (c) Bigfin reef squid Sepioteuthis lessonianademonstrating a slightly vertical ovoid pupil. (d) A cuttlefish species eyedemonstrating a W-shaped pupil. (a, b, d)—Courtesy of David G.Heidemann. (c)—Used with permission from Osman Temizel,Shutterstock.com2 Ophthalmology of Invertebrates 15http://shutterstock.comlight to a cut-off wavelength of 430 nm. Some octopus havebeen reported to have lenses that transmit light in the UVspectrum, and deep-dwelling cephalopods having transparentlenses (Denton and Warren 1968; Hanke and Kelber 2020).Unlike people where the lens shape is changed to allow foraccommodation (focusing), octopods move the entire lens toaccommodate.Retina, Vision, and OpticsCephalopods, with the exception of the nautilus, have a verywell-developed visual system. The nautilus has a rudimentarysingle-chambered “pinhole eye” with no lens and a smallpupil that acts to direct light onto the retina. The image isinverted and the small pupil opening only allows passage of asmall amount of light so that the images are dim. This type ofvision experience by the nautilus is in contrast to the single-chambered lens eyes of the Coleoid cephalopods (octopodsand decapods) that are quite advanced and similar to a humaneye (Fig. 2.6). The octopods do not use binocular visionmuch if at all (Wells 2013). Most decapods, in contrast, areable to use binocular vision.The retina of the cephalopod is relatively simple with thecomponents including photoreceptors and